Functional aspects of primary cilia in signaling, cell cycle and tumorigenesis

Cilia

Volumn 2, Issue 1, 2013, Pages

  Basten, Sander G ^a   Giles, Rachel H ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Cancer; Cell cycle; Cilia; Signal transduction

Indexed keywords

BETA CATENIN; CELL PROTEIN; PROTEIN HIPPO; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG; WNT PROTEIN;

CANCER GROWTH; CARCINOGENESIS; CELL CYCLE; CELL CYCLE REGULATION; CELL FUNCTION; CELL KINETICS; CELL MATURATION; CELL PROLIFERATION; CELL STRUCTURE; CENTROSOME; CHROMOSOMAL INSTABILITY; CILIARY DYSKINESIA; CILIARY MOTILITY; CILIOGENESIS; CILIOPATHY; DISEASE ASSOCIATION; DISEASES; EUKARYOTIC FLAGELLUM; FAMILIAL CANCER; FLOW MEASUREMENT; GENE MUTATION; HUMAN; KINETOSOME; METASTASIS; MICROTUBULE ASSEMBLY; MICROTUBULE ORGANIZING CENTER; PATHOPHYSIOLOGY; PHENOTYPE; PRESSURE SENSATION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; VIBRATION SENSE;

EID: 84888433372     PISSN: None     EISSN: 20462530     Source Type: Journal    
DOI: 10.1186/2046-2530-2-6     Document Type: Review

References (234)

1. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 2007, 8:880-893. 10.1038/nrm2278, 17955020.
2. Stearns T. Centrosome Duplication: A Centriolar Pas de Deux. Cell 2001, 145:417-420.
3. Schmidt KN, Kuhns S, Neuner A, Hub B, Zentgraf H, Pereira G. Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis. J Cell Biol 2012, 199:1083-1101. 10.1083/jcb.201202126, 23253480.
4. Dawe HR, Adams M, Wheway G, Szymanska K, Logan CV, Noegel AA, Gull K, Johnson CA. Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodeling of the actin cytoskeleton. J Cell Sci 2009, 122:2716-2726. 10.1242/jcs.043794, 2909318, 19596800.
5. Reiter JF, Blacque OE, Leroux MR. The base of the cilium: roles for transition fibers and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep 2012, 13:608-618. 10.1038/embor.2012.73, 22653444.
6. Kobayashi T, Tsang WY, Li J, Lane W, Dynlacht BD. Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis. Cell 2011, 145:914-925. 10.1016/j.cell.2011.04.028, 21620453.
7. Goetz SC, Liem KF, Anderson KV. The spinocerebellar ataxia-associated gene tau tubulin kinase-2 controls the initiation of ciliogenesis. Cell 2012, 151:847-858. 10.1016/j.cell.2012.10.010, 23141541.
8. Kim J, Lee JE, Heynen-Genel S, Suyama E, Ono K, Lee K, Ideker T, Aza-Blanc P, Gleeson JG. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 2010, 464:1048-1051. 10.1038/nature08895, 2929961, 20393563.
9. Schrøder JM, Larsen J, Komarova Y, Akhmanova A, Thorsteinsson RI, Grigoriev I, Manguso R, Christensen ST, Pedersen SF, Geimer S, Pedersen LB. EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. J Cell Sci 2011, 124:2539-2551. 10.1242/jcs.085852, 3138699, 21768326.
10. Hsiao Y-C, Tuz K, Ferland RJ. Trafficking in and to the primary cilium. Cilia 2012, 1:4. 10.1186/2046-2530-1-4, 3541539, 23351793.
11. Jin H, White SR, Shida T, Schulz S, Aguiar M, Gygi SP, Bazan JF, Nachury MV. The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 2012, 141:1208-1219.
12. Westlake CJ, Baye LM, Nachury MV, Wright KJ, Ervin KE, Phu L, Chalouni C, Beck JS, Kirkpatrick DS, Slusarski DC, Sheffield VC, Scheller RH, Jackson PK. Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome. Proc Natl Acad Sci 2011, 108:2759-2764. 10.1073/pnas.1018823108, 3041065, 21273506.
13. Ishikawa H, Marshall WF. Ciliogenesis: building the cell's antenna. Nat Rev Mol Cell Biol 2011, 12:222-234. 10.1038/nrm3085, 21427764.
14. Molla-Herman A, Ghossoub R, Blisnick T, Meunier A, Serres C, Silbermann F, Emmerson C, Romeo K, Bourdoncle P, Schmitt A, Saunier S, Spassky N, Bastin P, Benmerah A. The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia. J Cell Sci 2010, 123:1785-1795. 10.1242/jcs.059519, 20427320.
15. Benmerah A. The ciliary pocket. Curr Opin Cell Biol 2012, 25:1-7.
16. Yang J, Li T. The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos. Exp Cell Res 2005, 309:379-389. 10.1016/j.yexcr.2005.05.026, 16018997.
17. Garcia-Gonzalo FR, Reiter JF. Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J Cell Biol 2012, 197:697-709. 10.1083/jcb.201111146, 3373398, 22689651.
18. Kee HL, Dishinger JF, Lynne Blasius T, Liu CJ, Margolis B, Verhey KJ. A size-exclusion permeability barrier and nucleoporins characterize a ciliary pore complex that regulates transport into cilia. Nat Cell Biol 2012, 14:431-437. 10.1038/ncb2450, 3319646, 22388888.
19. Deane JA, Cole DG, Seeley ES, Diener DR, Rosenbaum JL. Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles. Curr Biol 2001, 11:1586-1590. 10.1016/S0960-9822(01)00484-5, 11676918.
20. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Sfakianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, OToole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi ARR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 2001, 145:513-528.
21. Williams CL, Li C, Kida K, Inglis PN, Mohan S, Semenec L, Bialas NJ, Stupay RM, Chen N, Blacque OE, Yoder BK, Leroux MR. MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J Cell Biol 2011, 192:1023-1041. 10.1083/jcb.201012116, 3063147, 21422230.
22. Valente EM, Logan CV, Mougou-Zerelli S, Lee JH, Silhavy JL, Brancati F, Iannicelli M, Travaglini L, Romani S, Illi B, Adams M, Szymanska K, Mazzotta A, Lee JE, Tolentino JC, Swistun D, Salpietro CD, Fede C, Gabriel S, Russ C, Cibulskis K, Sougnez C, Hildebrandt F, Otto EA, Held S, Diplas BH, Davis EE, Mikula M, Strom CM, Ben-Zeev B. Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 2010, 42:619-625. 10.1038/ng.594, 2894012, 20512146.
23. Huang L, Szymanska K, Jensen VL, Janecke AR, Innes AM, Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, Greenberg CR, McLeod DR, Bernier FP, Chudley AE, Müller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, Bell SM, Adkins J, Zuniga FI, Ross KD, Wang J, Ban MR, Becker C, Nurnberg P, Douglas S, Craft CM. TMEM237 is mutated in individuals with a Joubert syndrome-related disorder and expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet 2011, 89:713-730. 10.1016/j.ajhg.2011.11.005, 3234373, 22152675.
24. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, García-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF. A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. NPG 2011, 43:776-784.
25. Srour M, Hamdan FF, Schwartzentruber JA, Patry L, Ospina LH, Shevell MI, Désilets V, Dobrzeniecka S, Mathonnet G, Lemyre E, Massicotte C, Labuda D, Amrom D, Andermann E, Sébire G, Maranda B, Consortium FC, Rouleau GA, Majewski J, Michaud JL. Mutations in TMEM231 cause Joubert syndrome in French Canadians. J Med Genet 2012, 49:636-641. 10.1136/jmedgenet-2012-101132, 23012439.
26. Christopher KJ, Wang B, Kong Y, Weatherbee SD. Forward genetics uncovers Transmembrane protein 107 as a novel factor required for ciliogenesis and sonic hedgehog-signaling. Dev Biol 2012, 368:382-392. 10.1016/j.ydbio.2012.06.008, 22698544.
27. Hu Q, Milenkovic L, Jin H, Scott MP, Nachury MV, Spiliotis ET, Nelson WJ. A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 2012, 329:436-439.
28. Ward HH, Brown-Glaberman U, Wang J, Morita Y, Alper SL, Bedrick EJ, Gattone VH, Deretic D, Wandinger-Ness A. A conserved signal and GTPase complex are required for the ciliary transport of polycystin-1. Mol Biol Cell 2011, 22:3289-3305. 10.1091/mbc.E11-01-0082, 3172256, 21775626.
29. Follit JA, Li L, Vucica Y, Pazour GJ. The cytoplasmic tail of fibrocystin contains a ciliary-targeting sequence. J Cell Biol 2010, 188:21-28. 10.1083/jcb.200910096, 2812845, 20048263.
30. Dishinger JF, Kee HL, Jenkins PM, Fan S, Hurd TW, Hammond JW, Truong YN-T, Margolis B, Martens JR, Verhey KJ. Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-beta2 and RanGTP. Nat Cell Biol 2010, 12:703-710. 10.1038/ncb2073, 2896429, 20526328.
31. Mukhopadhyay S, Wen X, Ratti N, Loktev A, Rangell L, Scales SJ, Jackson PK. The ciliary G-protein-coupled receptor Gpr161 negatively regulates the sonic hedgehog pathway via cAMP-signaling. Cell 2013, 152:210-223. 10.1016/j.cell.2012.12.026, 23332756.
32. Wright KJ, Baye LM, Olivier-Mason A, Mukhopadhyay S, Sang L, Kwong M, Wang W, Pretorius PR, Sheffield VC, Sengupta P, Slusarski DC, Jackson PK. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev 2011, 25:2347-2360. 10.1101/gad.173443.111, 3222901, 22085962.
33. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002, 3:813-825. 10.1038/nrm952, 12415299.
34. Verhey KJ, Dishinger J, Kee HL. Kinesin motors and primary cilia. Biochem Soc Trans 2011, 39:1120-1125. 10.1042/BST0391120, 3538878, 21936775.
35. Liem KF, Ashe A, He M, Satir P, Moran J, Beier D, Wicking C, Anderson KV. The IFT-A complex regulates Shh-signaling through cilia structure and membrane protein trafficking. J Cell Biol 2012, 197:789-800. 10.1083/jcb.201110049, 3373400, 22689656.
36. Zhao C, Omori Y, Brodowska K, Kovach P, Malicki J. Kinesin-2 family in vertebrate ciliogenesis. Proc Natl Acad Sci 2012, 109:2388-2393. 10.1073/pnas.1116035109, 3289367, 22308397.
37. Insinna C, Pathak N, Perkins B, Drummond I, Besharse JC. The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development. Dev Biol 2008, 316:160-170. 10.1016/j.ydbio.2008.01.025, 2362383, 18304522.
38. Peden EM, Barr MM. The KLP-6 kinesin is required for male mating behaviors and polycystin localization in Caenorhabditis elegans. Curr Biol 2005, 15:394-404.
39. Liem KF, He M, Ocbina PJR, Anderson KV. Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog-signaling. Proc Natl Acad Sci 2009, 106:13377-13382. 2726420, 19666503.
40. Oh EC, Katsanis N. Cilia in vertebrate development and disease. Development 2012, 139:443-448. 10.1242/dev.050054, 3275291, 22223675.
41. van Asselt SJ, de Vries EG, van Dullemen HM, Brouwers AH, Walenkamp AM, Giles RH, Links TP. Pancreatic cyst development: insights from von Hippel-Lindau disease. Cilia 2013, 2:3. 10.1186/2046-2530-2-3, 3579754, 23384121.
42. Louvi A, Grove EA. Cilia in the CNS: the quiet organelle claims center stage. Neuron 2011, 69:1046-1060. 10.1016/j.neuron.2011.03.002, 3070490, 21435552.
43. Geerts WJC, Vocking K, Schoonen N, Haarbosch L, van Donselaar EG, Regan-Klapisz E, Post JA. Cobblestone HUVECs: a human model system for studying primary ciliogenesis. J Struct Biol 2011, 176:350-359. 10.1016/j.jsb.2011.09.013, 22001693.
44. Finetti F, Paccani SR, Rosenbaum J, Baldari CT. Intraflagellar transport: a new player at the immune synapse. Trends Immunol 2011, 32:139-145. 10.1016/j.it.2011.02.001, 21388881.
45. Hirokawa N, Tanaka Y, Okada Y, Takeda S. Nodal flow and the generation of left-right asymmetry. Cell 2006, 125:33-45. 10.1016/j.cell.2006.03.002, 16615888.
46. Tobin JL, Beales PL. The nonmotile ciliopathies. Genet Med 2009, 11:386-402. 10.1097/GIM.0b013e3181a02882, 19421068.
47. Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB, Cole DG. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol 2000, 151:709-718. 10.1083/jcb.151.3.709, 2185580, 11062270.
48. http://www.ifcbiol.org/Primaryciliumweb/.
49. Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 2011, 26:1039-1056. 10.1007/s00467-010-1731-7, 3098370, 21210154.
50. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med 2011, 364:1533-1543. 10.1056/NEJMra1010172, 3640822, 21506742.
51. DAngelo A, Franco B. The primary cilium in different tissues-lessons from patients and animal models. Pediatr Nephrol 2011, 26:655-662. 10.1007/s00467-010-1650-7, 20890766.
52. Bredrup C, Saunier S, Oud MM, Fiskerstrand T, Hoischen A, Brackman D, Leh SM, Midtbø M, Filhol E, Bole-Feysot C, Nitschké P, Gilissen C, Haugen OH, Sanders J-SF, Stolte-Dijkstra I, Mans DA, Steenbergen EJ, Hamel BCJ, Matignon M, Pfundt R, Jeanpierre C, Boman H, Rødahl E, Veltman JA, Knappskog PM, Knoers NVAM, Roepman R, Arts HH. Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-a gene WDR19. Am J Hum Genet 2011, 89:634-643. 10.1016/j.ajhg.2011.10.001, 3213394, 22019273.
53. DAngelo A, Franco B. The dynamic cilium in human diseases. Pathogenetics 2009, 2:3. 10.1186/1755-8417-2-3, 2694804, 19439065.
54. Marley A, von Zastrow M. A simple cell-based assay reveals that diverse neuropsychiatric risk genes converge on primary cilia. PLoS One 2012, 7:e46647. 10.1371/journal.pone.0046647, 3463515, 23056384.
55. Leigh MW, Pittman JE, Carson JL, Ferkol TW, Dell SD, Davis SD, Knowles MR, Zariwala MA. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet Med 2009, 11:473-487. 10.1097/GIM.0b013e3181a53562, 19606528.
56. Gherman A, Davis EE, Katsanis N. The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat Genet 2006, 38:961-962. 10.1038/ng0906-961, 16940995.
57. Davis EE, Katsanis N. The ciliopathies: a transitional model into systems biology of human genetic disease. Curr Opin Genet Dev 2012, 22:290-303. 10.1016/j.gde.2012.04.006, 22632799.
58. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AEH, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 2003, 33:129-137. 10.1038/ng1076, 12514735.
59. Ward CJ, Yuan D, Masyuk TV, Wang X, Punyashthiti R, Whelan S, Bacallao R, Torra R, LaRusso NF, Torres VE, Harris PC. Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia. Hum Mol Genet 2003, 12:2703-2710. 10.1093/hmg/ddg274, 12925574.
60. Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T. Polycystin-1, STAT6, and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 2006, 10:57-69. 10.1016/j.devcel.2005.12.005, 16399078.
61. Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med 2007, 13:1490-1495. 10.1038/nm1675, 2302790, 17965720.
62. Abdul-Majeed S, Nauli SM. Calcium-mediated mechanisms of cystic expansion. BBA - Molecular Basis of Disease 2011, 10:1281-1290.
63. Pietrobon M, Zamparo I, Maritan M, Franchi SA, Pozzan T, Lodovichi C. Interplay among cGMP, cAMP, and Ca2+ in living olfactory sensory neurons in vitro and in vivo. J Neurosci 2011, 31:8395-8405. 10.1523/JNEUROSCI.6722-10.2011, 21653844.
64. Kotsis F, Boehlke C, Kuehn EW. The ciliary flow sensor and polycystic kidney disease. Nephrol Dial Transplant 2013, 3:518-526.
65. Hoey DA, Downs ME, Jacobs CR. The mechanics of the primary cilium: an intricate structure with complex function. J Biomech 2012, 45:17-26. 10.1016/j.jbiomech.2011.08.008, 3242821, 21899847.
66. Prodromou NV, Thompson CL, Osborn DPS, Cogger KF, Ashworth R, Knight MM, Beales PL, Chapple JP. Heat shock induces rapid resorption of primary cilia. J Cell Sci 2012, 125:4297-4305. 10.1242/jcs.100545, 3516438, 22718348.
67. Wang Y, McMahon AP, Allen BL. Shifting paradigms in hedgehog-signaling. Curr Opin Cell Biol 2007, 19:159-165. 10.1016/j.ceb.2007.02.005, 17303409.
68. Tasouri E, Tucker KL. Primary cilia and organogenesis: is hedgehog the only sculptor?. Cell Tissue Res 2011, 345:21-40. 10.1007/s00441-011-1192-8, 21638207.
69. Goetz SC, Anderson KV. The primary cilium: a signaling center during vertebrate development. Nat Rev Genet 2010, 11:331-344. 10.1038/nrg2774, 3121168, 20395968.
70. Tukachinsky H, Lopez LV, Salic A. A mechanism for vertebrate hedgehog- signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes. J Cell Biol 2010, 191:415-428. 10.1083/jcb.201004108, 2958481, 20956384.
71. Robbins DJ, Fei DL, Riobo NA. The hedgehog signal transduction network. Sci Signal 2012, 5:re6. 10.1126/scisignal.2002906, 23074268.
72. Wang B, Li Y. Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing. Proc Natl Acad Sci USA 2006, 103:33-38. 10.1073/pnas.0509927103, 1325010, 16371461.
73. Chen M-H, Wilson CW, Li Y-J, Law KKL, Lu C-S, Gacayan R, Zhang X, Hui C-C, Chuang P-T. Cilium-independent regulation of Gli protein function by Sufu in hedgehog-signaling is evolutionarily conserved. Genes Dev 2009, 23:1910-1928. 10.1101/gad.1794109, 2725943, 19684112.
74. Humke EW, Dorn KV, Milenkovic L, Scott MP, Rohatgi R. The output of hedgehog-signaling is controlled by the dynamic association between suppressor of fused and the Gli proteins. Genes Dev 2010, 24:670-682. 10.1101/gad.1902910, 2849124, 20360384.
75. Huangfu D, Liu A, Rakeman AS, Murcia NS, Niswander L, Anderson KV. Hedgehog-signaling in the mouse requires intraflagellar transport proteins. Nature 2003, 426:83-87. 10.1038/nature02061, 14603322.
76. Liu A, Wang B, Niswander LA. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors. Development 2005, 132:3103-3111. 10.1242/dev.01894, 15930098.
77. May SR, Ashique AM, Karlen M, Wang B, Shen Y, Zarbalis K, Reiter J, Ericson J, Peterson AS. Loss of the retrograde motor for IFT disrupts localization of Smo to cilia and prevents the expression of both activator and repressor functions of Gli. Dev Biol 2005, 287:378-389. 10.1016/j.ydbio.2005.08.050, 16229832.
78. Cortellino S, Wang C, Wang B, Bassi MR, Caretti E, Champeval D, Calmont A, Jarnik M, Burch J, Zaret KS, Larue L, Bellacosa A. Defective ciliogenesis, embryonic lethality and severe impairment of the sonic hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4. Dev Biol 2009, 325:225-237. 10.1016/j.ydbio.2008.10.020, 2645042, 19000668.
79. Tran PV, Haycraft CJ, Besschetnova TY, Turbe-Doan A, Stottmann RW, Herron BJ, Chesebro AL, Qiu H, Scherz PJ, Shah JV, Yoder BK, Beier DR. THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet 2008, 40:403-410. 10.1038/ng.105, 18327258.
80. Gao C, Chen Y-G. Dishevelled: the hub of Wnt-signaling. Cell Signal 2010, 22:717-727. 10.1016/j.cellsig.2009.11.021, 20006983.
81. Gerdes JM, Liu Y, Zaghloul NA, Leitch CC, Lawson SS, Kato M, Beachy PA, Beales PL, DeMartino GN, Fisher S, Badano JL, Katsanis N. Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat Genet 2007, 39:1350-1360. 10.1038/ng.2007.12, 17906624.
82. Corbit KC, Shyer AE, Dowdle WE, Gaulden J, Singla V, Reiter JF. Kif3a constrains β-catenin-dependent Wnt-signalling through dual ciliary and non-ciliary mechanisms. Nat Cell Biol 2007, 10:70-76.
83. Voronina VA, Takemaru K-I, Treuting P, Love D, Grubb BR, Hajjar AM, Adams A, Li F-Q, Moon RT. Inactivation of Chibby affects function of motile airway cilia. J Cell Biol 2009, 185:225-233. 10.1083/jcb.200809144, 2700371, 19364920.
84. Kishimoto N, Cao Y, Park A, Sun Z. Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways. Dev Cell 2008, 14:954-961. 10.1016/j.devcel.2008.03.010, 18539122.
85. Otto EA, Schermer B, Obara T, OToole JF, Hiller KS, Mueller AM, Ruf RG, Hoefele J, Beekmann F, Landau D, Foreman JW, Goodship JA, Strachan T, Kispert A, Wolf MT, Gagnadoux MF, Nivet H, Antignac C, Walz G, Drummond IA, Benzing T, Hildebrandt F. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet 2003, 34:413-420. 10.1038/ng1217, 12872123.
86. Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Krönig C, Schermer B, Benzing T, Cabello OA, Jenny A, Mlodzik M, Polok B, Driever W, Obara T, Walz G. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt-signaling pathways. Nat Genet 2005, 37:537-543. 10.1038/ng1552, 15852005.
87. Saadi-Kheddouci S, Berribe D, Romagnolo B, Cluzeaud F, Peuchmaur M, Kahn A, Vandewalle A, Perret C. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the b-catenin gene. Oncogene 2001, 42:5972-5981.
88. Lancaster MA, Schroth J, Gleeson JG. Subcellular spatial regulation of canonical Wnt-signalling at the primary cilium. Nat Cell Biol 2011, 13:702-709.
89. Lancaster MA, Louie CM, Silhavy JL, Sintasath L, DeCambre M, Nigam SK, Willert K, Gleeson JG. Impaired Wnt-beta-catenin-signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy. Nat Med 2009, 15:1046-1054. 10.1038/nm.2010, 2895985, 19718039.
90. Ocbina PJR, Tuson M, Anderson KV. Primary cilia are not required for normal canonical Wnt-signaling in the mouse embryo. PLoS One 2009, 4:e6839. 10.1371/journal.pone.0006839, 2729396, 19718259.
91. Huang P, Schier AF. Dampened hedgehog-signaling but normal Wnt- signaling in zebrafish without cilia. Development 2009, 136:3089-3098. 10.1242/dev.041343, 2730366, 19700616.
92. Chang C-F, Serra R. Ift88 regulates hedgehog-signaling, Sfrp5 expression, and β-catenin activity in post-natal growth plate. J Orthop Res 2012, 3:350-356.
93. Habas R, Dawid IB. Dishevelled and Wnt-signaling: is the nucleus the final frontier?. J Biol 2005, 4:2. 10.1186/jbiol22, 551522, 15720723.
94. Happé H, de Heer E, Peters DJM. Polycystic kidney disease: the complexity of planar cell polarity and signaling during tissue regeneration and cyst formation. Biochim Biophys Acta 2011, 10:1249-1255.
95. Wallingford JB, Mitchell B. Strange as it may seem: the many links between Wnt-signaling, planar cell polarity, and cilia. Genes Dev 2011, 25:201-213. 10.1101/gad.2008011, 3034894, 21289065.
96. Delaval B, Bright A, Lawson ND, Doxsey S. The cilia protein IFT88 is required for spindle orientation in mitosis. Nat Cell Biol 2011, 13:461-468. 10.1038/ncb2202, 3073523, 21441926.
97. Singla V, Romaguera-Ros M, García-Verdugo JM, Reiter JF. Ofd1, a human disease gene, regulates the length and distal structure of centrioles. Dev Cell 2010, 18:410-424. 10.1016/j.devcel.2009.12.022, 2841064, 20230748.
98. Kim JC, Badano JL, Sibold S, Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, Ross AJ, Leroux MR, Katsanis N, Beales PL. The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat Genet 2004, 36:462-470. 10.1038/ng1352, 15107855.
99. Park TJ, Mitchell BJ, Abitua PB, Kintner C, Wallingford JB. Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells. Nat Genet 2008, 40:871-879. 10.1038/ng.104, 2771675, 18552847.
100. Hoch RV, Soriano P. Roles of PDGF in animal development. Development 2003, 130:4769-4784. 10.1242/dev.00721, 12952899.
101. Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST. PDGFRαα-signaling is regulated through the primary cilium in fibroblasts. Curr Biol 2005, 15:1861-1866. 10.1016/j.cub.2005.09.012, 16243034.
102. Schneider L, Cammer M, Lehman J, Nielsen SK, Guerra CF, Veland IR, Stock C, Hoffmann EK, Yoder BK, Schwab A, Satir P, Christensen ST. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem 2010, 25:279-292. 10.1159/000276562, 2924811,2924811, 20110689.
103. Christensen ST, Clement CA, Satir P, Pedersen LB. Primary cilia and coordination of receptor tyrosine kinase (RTK)-signaling. J Pathol 2012, 226:172-184. 10.1002/path.3004, 21956154.
104. Neugebauer JM, Amack JD, Peterson AG, Bisgrove BW, Yost HJ. FGF-signaling during embryo development regulates cilia length in diverse epithelia. Nature 2009, 458:651-654. 10.1038/nature07753, 2688717, 19242413.
105. Harvey K, Tapon N. The Salvador-Warts-Hippo pathway - an emerging tumor-suppressor network. Nat Rev Cancer 2007, 7:182-191. 10.1038/nrc2070, 17318211.
106. Habbig S, Bartram MP, Müller RU, Schwarz R, Andriopoulos N, Chen S, Sägmüller JG, Hoehne M, Burst V, Liebau MC, Reinhardt HC, Benzing T, Schermer B. NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway. J Cell Biol 2011, 193:633-642. 10.1083/jcb.201009069, 3166863, 21555462.
107. Grusche FA, Richardson HE, Harvey KF. Upstream regulation of the hippo size control pathway. Curr Biol 2012, 20:R574-R582.
108. Sfakianos J, Togawa A, Maday S, Hull M, Pypaert M, Cantley L, Toomre D, Mellman I. Par3 functions in the biogenesis of the primary cilium in polarized epithelial cells. J Cell Biol 2007, 179:1133-1140. 10.1083/jcb.200709111, 2140027, 18070914.
109. Tavares A, Gonçalves J, Florindo C, Tavares AA, Soares H. Mob1: defining cell polarity for proper cell division. J Cell Sci 2012, 125:516-527. 10.1242/jcs.096610, 22331360.
110. Happé H, van der Wal AM, Leonhard WN, Kunnen SJ, Breuning MH, de Heer E, Peters DJM. Altered Hippo-signaling in polycystic kidney disease. J Pathol 2011, 224:133-142. 10.1002/path.2856, 21381034.
111. Egorova AD, Khedoe PPSJ, Goumans M-JTH, Yoder BK, Nauli SM, ten Dijke P, Poelmann RE, Hierck BP. Lack of primary cilia primes shear-induced endothelial-to-mesenchymal transition. Circ Res 2011, 108:1093-1101. 10.1161/CIRCRESAHA.110.231860, 3094764, 21393577.
112. Ezratty EJ, Stokes N, Chai S, Shah AS, Williams SE, Fuchs E. A role for the primary cilium in Notch-signaling and epidermal differentiation during skin development. Cell 2011, 145:1129-1141. 10.1016/j.cell.2011.05.030, 3135909, 21703454.
113. Mukhopadhyay S, Jackson PK. The tubby family proteins. Genome Biol 2011, 12:225. 10.1186/gb-2011-12-6-225, 3218838, 21722349.
114. Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compere P, Schiffmann SN, Gergely F, Riley JH, Perez-Morga D, Woods CG, Schurmans S. INPP5E mutations cause primary cilium-signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet 2009, 41:1027-1031. 10.1038/ng.427, 19668215.
115. Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO. Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol-signaling to the ciliopathies. Nat Genet 2009, 41:1032-1036. 10.1038/ng.423, 2746682, 19668216.
116. Nigg EA, Stearns T. The centrosome cycle: centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol 2011, 13:1154-1160. 10.1038/ncb2345, 21968988.
117. Kulaga HM, Leitch CC, Eichers ER, Badano JL, Lesemann A, Hoskins BE, Lupski JR, Beales PL, Reed RR, Katsanis N. Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet 2004, 36:994-998. 10.1038/ng1418, 15322545.
118. Fath MA, Mullins RF, Searby C, Nishimura DY, Wei J, Rahmouni K, Davis RE, Tayeh MK, Andrews M, Yang B, Sigmund CD, Stone EM, Sheffield VC. Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. Hum Mol Genet 2005, 14:1109-1118. 10.1093/hmg/ddi123, 15772095.
119. Kim JC, Ou YY, Badano JL, Esmail MA, Leitch CC, Fiedrich E, Beales PL, Archibald JM, Katsanis N, Rattner JB, Leroux MR. MKKS/BBS6, a divergent chaperonin-like protein linked to the obesity disorder Bardet-Biedl syndrome, is a novel centrosomal component required for cytokinesis. J Cell Sci 2005, 118:1007-1020. 10.1242/jcs.01676, 15731008.
120. Robert A, Margall-Ducos G, Guidotti J-E, Brégerie O, Celati C, Bréchot C, Desdouets C. The intraflagellar transport component IFT88/polaris is a centrosomal protein regulating G1-S transition in non-ciliated cells. J Cell Sci 2007, 120:628-637. 10.1242/jcs.03366, 17264151.
121. Richards WG, Yoder BK, Isfort RJ, Detilleux PG, Foster C, Neilsen N, Woychik RP, Wilkinson JE. Oval cell proliferation associated with the murine insertional mutation TgN737Rpw. Am J Pathol 1996, 149:1919-1930. 1865369, 8952527.
122. Zhang Q, Davenport JR, Croyle MJ, Haycraft CJ, Yoder BK. Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737(orpk) mutant mice. Lab Invest 2005, 85:45-64.
123. Qin H, Wang Z, Diener D, Rosenbaum J. Intraflagellar transport protein 27 is a small G protein involved in cell-cycle control. Curr Biol 2007, 17:193-202. 10.1016/j.cub.2006.12.040, 1905864, 17276912.
124. Wood CR, Wang Z, Diener D, Zones JM, Rosenbaum J, Umen JG. IFT proteins accumulate during cell division and localize to the cleavage furrow in Chlamydomonas. PLoS One 2012, 7:e30729. 10.1371/journal.pone.0030729, 3273483, 22328921.
125. Satir P, Mitchell DR, Jékely G. How did the cilium evolve?. Curr Top Dev Biol 2008, 85:63-82.
126. Smith KR, Kieserman EK, Wang PI, Basten SG, Giles RH, Marcotte EM, Wallingford JB. A role for central spindle proteins in cilia structure and function. Cytoskeleton 2011, 68:112-124. 10.1002/cm.20498, 21246755.
127. Plotnikova OV, Golemis EA, Pugacheva EN. Cell cycle-dependent ciliogenesis and cancer. Cancer Res 2008, 68:2058-2061. 10.1158/0008-5472.CAN-07-5838, 2546565, 18381407.
128. Mikule K, Delaval B, Kaldis P, Jurcyzk A, Hergert P, Doxsey S. Loss of centrosome integrity induces p38-p53-p21-dependent G1-S arrest. Nat Cell Biol 2007, 9:160-170. 10.1038/ncb1529, 17330329.
129. Plotnikova OV, Pugacheva EN, Golemis EA. Primary cilia and the cell cycle. Methods Cell Biol 2009, 94:137-160. 2852269, 20362089.
130. Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007, 129:1351-1363. 10.1016/j.cell.2007.04.035, 2504417, 17604723.
131. Kinzel D, Boldt K, Davis EE, Burtscher I, Trümbach D, Diplas B, Attié-Bitach T, Wurst W, Katsanis N, Ueffing M, Lickert H. Pitchfork regulates primary cilia disassembly and left-right asymmetry. Dev Cell 2010, 19:66-77. 10.1016/j.devcel.2010.06.005, 20643351.
132. Li Y, Bavarva JH, Wang Z, Guo J, Qian C, Thibodeau SN, Golemis EA, Liu W. HEF1, a novel target of Wnt-signaling, promotes colonic cell migration and cancer progression. Oncogene 2011, 30:2633-2643. 10.1038/onc.2010.632, 3164309, 21317929.
133. Lee KH, Johmura Y, Yu L-R, Park J-E, Gao Y, Bang JK, Zhou M, Veenstra TD, Yeon Kim B, Lee KS. Identification of a novel Wnt5a-CK1ε-Dvl2-Plk1-mediated primary cilia disassembly pathway. EMBO J 2012, 31:3104-3117. 10.1038/emboj.2012.144, 22609948.
134. Spalluto C, Wilson DI, Hearn T. Nek2 localises to the distal portion of the mother centriole/basal body and is required for timely cilium disassembly at the G2/M transition. Eur J Cell Biol 2012, 91:675-686. 10.1016/j.ejcb.2012.03.009, 22613497.
135. Tsang WY, Bossard C, Khanna H, Peränen J, Swaroop A, Malhotra V, Dynlacht BD. CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev Cell 2008, 15:187-197. 10.1016/j.devcel.2008.07.004, 18694559.
136. Spektor A, Tsang WY, Khoo D, Dynlacht BD. Cep97 and CP110 suppress a cilia assembly program. Cell 2007, 130:678-690. 10.1016/j.cell.2007.06.027, 17719545.
137. Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sánchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell 2006, 17:3423-3434. 10.1091/mbc.E06-04-0371, 1525247, 16760425.
138. Humbert MC, Weihbrecht K, Searby CC, Li Y, Pope RM, Sheffield VC, Seo S. ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proc Natl Acad Sci 2012, 109:19691-19696. 10.1073/pnas.1210916109, 23150559.
139. Jackson PK. Do cilia put brakes on the cell cycle?. Nat Cell Biol 2011, 13:340-342. 10.1038/ncb0411-340, 21460803.
140. Kim S, Zaghloul NA, Bubenshchikova E, Oh EC, Rankin S, Katsanis N, Obara T, Tsiokas L. Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol 2011, 13:351-360. 10.1038/ncb2183, 3077088, 21394081.
141. Li A, Saito M, Chuang J-Z, Tseng Y-Y, Dedesma C, Tomizawa K, Kaitsuka T, Sung C-H. Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 2011, 13:402-411. 10.1038/ncb2218, 21394082.
142. Besschetnova TY, Kolpakova-Hart E, Guan Y, Zhou J, Olsen BR, Shah JV. Identification of signaling pathways regulating primary cilium length and flow-mediated adaptation. Curr Biol 2010, 20:182-187. 10.1016/j.cub.2009.11.072, 2990526, 20096584.
143. Wang W, Brautigan DL. Phosphatase inhibitor 2 promotes acetylation of tubulin in the primary cilium of human retinal epithelial cells. BMC Cell Biol 2008, 9:62. 10.1186/1471-2121-9-62, 2630314, 19036150.
144. Abdul-Majeed S, Nauli SM. Dopamine receptor type 5 in the primary cilia has dual chemo- and mechano-sensory roles. Hypertension 2011, 58:325-331. 10.1161/HYPERTENSIONAHA.111.172080, 3150550, 21709211.
145. Avasthi P, Marley A, Lin H, Gregori-Puigjane E, Shoichet BK, von Zastrow M, Marshall WF. A chemical screen identifies class a G protein-coupled receptors as regulators of cilia. ACS Chem Biol 2012, 7:911-919. 10.1021/cb200349v, 22375814.
146. Haug K, Khan S, Fuchs S, König R. OFD II, OFD VI, and Joubert syndrome manifestations in two sibs. Am J Med Genet 2000, 91:135-137. 10.1002/(SICI)1096-8628(20000313)91:2<135::AID-AJMG11>3.0.CO;2-1, 10748413.
147. Brancati F, Dallapiccola B, Valente EM. Joubert Syndrome and related disorders. Orphanet J Rare Dis 2010, 5:20. 10.1186/1750-1172-5-20, 2913941, 20615230.
148. Beales PL, Reid HA, Griffiths MH, Maher ER, Flinter FA, Woolf AS. Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome. Nephrol Dial Transplant 2000, 15:1977-1985. 10.1093/ndt/15.12.1977, 11096143.
149. Hjortshøj TD, Grønskov K, Rosenberg T, Brøndum-Nielsen K, Olsen JH. Risk for cancer in patients with Bardet-Biedl syndrome and their relatives. Am J Med Genet A 2007, 143A:1699-1702. 10.1002/ajmg.a.31805, 17587209.
150. García-Zaragoza E, Pérez-Tavarez R, Ballester A, Lafarga V, Jiménez-Reinoso A, Ramírez T, Murillas R, Gallego MI. Intraepithelial paracrine hedgehog-signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland. Dev Biol 2012, 372:28-44. 10.1016/j.ydbio.2012.09.005, 23000969.
151. Hassounah NB, Bunch TA, McDermott KM. Molecular pathways: the role of primary cilia in cancer progression and therapeutics with a focus on hedgehog- signaling. Clin Cancer Res 2012, 18:2429-2435. 10.1158/1078-0432.CCR-11-0755, 22415315.
152. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JKV, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PVK. The genomic landscapes of human breast and colorectal cancers. Science 2007, 318:1108-1113. 10.1126/science.1145720, 17932254.
153. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JKV, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314:268-274. 10.1126/science.1133427, 16959974.
154. Yuan K, Frolova N, Xie Y, Wang D, Cook L, Kwon Y-J, Steg AD, Serra R, Frost AR. Primary cilia are decreased in breast cancer: analysis of a collection of human breast cancer cell lines and tissues. J Histochem Cytochem 2010, 58:857-870. 10.1369/jhc.2010.955856, 2942739, 20530462.
155. McDermott KM, Liu BY, Tlsty TD, Pazour GJ. Primary cilia regulate branching morphogenesis during mammary gland development. Curr Biol 2010, 20:731-737. 10.1016/j.cub.2010.02.048, 2916967, 20381354.
156. Bowers AJ, Boylan JF. Nek8, a NIMA family kinase member, is overexpressed in primary human breast tumors. Gene 2004, 328:135-142.
157. Habbig S, Bartram MP, Sägmüller JG, Griessmann A, Franke M, Müller R-U, Schwarz R, Hoehne M, Bergmann C, Tessmer C, Reinhardt HC, Burst V, Benzing T, Schermer B. The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ. Hum Mol Genet 2012, 21:5528-5538. 10.1093/hmg/dds408, 23026745.
158. Kim J, Dabiri S, Seeley ES. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma. PLoS One 2011, 6:e27410. 10.1371/journal.pone.0027410, 3214062, 22096570.
159. Seeley ES, Carrière C, Goetze T, Longnecker DS, Korc M. Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res 2009, 69:422-430. 10.1158/0008-5472.CAN-08-1290, 2629528, 19147554.
160. Egeberg DL, Lethan M, Manguso R, Schneider L, Awan A, Jørgensen TS, Byskov AG, Pedersen LB, Christensen ST. Primary cilia and aberrant cell-signaling in epithelial ovarian cancer. Cilia 2012, 1:15. 10.1186/2046-2530-1-15, 3555760, 23351307.
161. Bezginov A, Clark GW, Charlebois RL, Dar V-U-N, Tillier ERM. Coevolution reveals a network of human proteins originating with multicellularity. Mol Biol Evol 2012, 30:332-346. 3548307, 22977115.
162. Basten SG, Davis EE, Gillis AJM, van Rooijen E, Stoop H, Babala N, Logister I, Heath ZG, Jonges TN, Katsanis N, Voest E, van Eeden FJ, Medema RH, Ketting RF, Schulte-Merker S, Looijenga LHJ, Giles RH. Mutations in LRRC50 predispose zebrafish and humans to seminomas. PLoS Genet 2013, 9:e1003384. 10.1371/journal.pgen.1003384, 3627517, 23599692.
163. Santos N, Reiter JF. Building it up and taking it down: the regulation of vertebrate ciliogenesis. Dev Dyn 2008, 237:1972-1981. 10.1002/dvdy.21540, 3304540, 18435467.
164. Mans DA, Voest EE, Giles RH. All along the watchtower: is the cilium a tumor suppressor organelle?. BBA - Reviews on Cancer 2008, 1786:114-125.
165. Wong SY, Seol AD, So P-L, Ermilov AN, Bichakjian CK, Epstein EH, Dlugosz AA, Reiter JF. Primary cilia can both mediate and suppress hedgehog pathway-dependent tumorigenesis. Nat Med 2009, 15:1055-1061. 10.1038/nm.2011, 2895420, 19701205.
166. Han Y-G, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A. Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 2009, 15:1062-1065. 10.1038/nm.2020, 2771737, 19701203.
167. Toftgård R. Two sides to cilia in cancer. Nat Med 2009, 15:994-996. 10.1038/nm0909-994, 19734870.
168. Scales SJ, de Sauvage FJ. Mechanisms of hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 2009, 30:303-312. 10.1016/j.tips.2009.03.007, 19443052.
169. Bonsib SM. Renal cystic diseases and renal neoplasms: a mini-review. Clin J Am Soc Nephrol 2009, 4:1998-2007. 10.2215/CJN.02020309, 19875768.
170. Rookmaaker MB, van Gerven HAJM, Goldschmeding R, Boer WH. Solid renal tumors of collecting duct origin in patients on chronic lithium therapy. Clin Kidney J 2012, 5:412-415.
171. Takahashi M, Yang XJ, Sugimura J, Backdahl J, Tretiakova M, Qian C-N, Gray SG, Knapp R, Anema J, Kahnoski R, Nicol D, Vogelzang NJ, Furge KA, Kanayama H, Kagawa S, Teh BT. Molecular subclassification of kidney tumors and the discovery of new diagnostic markers. Oncogene 2003, 22:6810-6818. 10.1038/sj.onc.1206869, 14555994.
172. Klomp JA, Petillo D, Niemi NM, Dykema KJ, Chen J, Yang XJ, Sääf A, Zickert P, Aly M, Bergerheim U, Nordenskjöld M, Gad S, Giraud S, Denoux Y, Yonneau L, Méjean A, Vasiliu V, Richard S, MacKeigan JP, Teh BT, Furge KA. Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression. BMC Med Genomics 2010, 3:59. 10.1186/1755-8794-3-59, 3012009, 21162720.
173. Yusenko MV. Molecular pathology of chromophobe renal cell carcinoma: a review. Int J Urol 2010, 17:592-600. 10.1111/j.1442-2042.2010.02558.x, 20590942.
174. Yusenko MV. Molecular pathology of renal oncocytoma: a review. Int J Urol 2010, 17:602-612. 10.1111/j.1442-2042.2010.02574.x, 20590944.
175. Schraml P, Frew IJ, Thoma CR, Boysen G, Struckmann K, Krek W, Moch H. Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia. Mod Pathol 2008, 22:31-36.
176. Basten SG, Willekers S, Vermaat J, Slaats G. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue. Cilia 2013, 2:2. 10.1186/2046-2530-2-2, 3564780, 23369289.
177. Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F, Drabkin HA. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci USA 1998, 95:9572-9577. 10.1073/pnas.95.16.9572, 21380, 9689122.
178. Adam MP, Frantzen C, Links TP, Giles RH. von Hippel-Lindau Disease. 2000,
179. Moore LE, Nickerson ML, Brennan P, Toro JR, Jaeger E, Rinsky J, Han SS, Zaridze D, Matveev V, Janout V, Kollarova H, Bencko V, Navratilova M, Szeszenia-Dabrowska N, Mates D, Schmidt LS, Lenz P, Karami S, Linehan WM, Merino M, Chanock S, Boffetta P, Chow W-H, Waldman FM, Rothman N. von Hippel-Lindau (VHL) inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors. PLoS Genet 2011, 7:e1002312. 10.1371/journal.pgen.1002312, 3192834, 22022277.
180. Kaelin WG. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002, 2:673-682. 10.1038/nrc885, 12209156.
181. Kim WY, Safran M, Buckley MRM, Ebert BL, Glickman J, Bosenberg M, Regan M, Kaelin WG. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J 2006, 25:4650-4662. 10.1038/sj.emboj.7601300, 1589988, 16977322.
182. Schermer B, Ghenoiu C, Bartram M, Müller R-U, Kotsis F, Höhne M, Kühn W, Rapka M, Nitschke R, Zentgraf H, Fliegauf M, Omran H, Walz G, Benzing T. The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth. J Cell Biol 2006, 175:547-554. 10.1083/jcb.200605092, 2064591, 17101696.
183. Thoma CR, Frew IJ, Hoerner CR, Montani M, Moch H, Krek W. pVHL and GSK3beta are components of a primary cilium-maintenance signaling network. Nat Cell Biol 2007, 9:588-595. 10.1038/ncb1579, 17450132.
184. Frew IJ, Thoma CR, Georgiev S, Minola A, Hitz M, Montani M, Moch H, Krek W. pVHL and PTEN tumor suppressor proteins cooperatively suppress kidney cyst formation. EMBO J 2008, 27:1747-1757. 10.1038/emboj.2008.96, 2435131, 18497742.
185. Thoma CR, Toso A, Gutbrodt KL, Reggi SP, Frew IJ, Schraml P, Hergovich A, Moch H, Meraldi P, Krek W. VHL loss causes spindle misorientation and chromosome instability. Nat Cell Biol 2009, 11:994-1001. 10.1038/ncb1912, 19620968.
186. Hartman TR, Liu D, Zilfou JT, Robb V, Morrison T, Watnick T, Henske EP. The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway. Hum Mol Genet 2008, 18:151-163. 10.1093/hmg/ddn325, 2644647, 18845692.
187. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006, 355:1345-1356. 10.1056/NEJMra055323, 17005952.
188. Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 2001, 68:64-80. 10.1086/316951, 1234935, 11112665.
189. Wilson C. A mouse model of tuberous sclerosis 1 showing background specific early post-natal mortality and metastatic renal cell carcinoma. Hum Mol Genet 2005, 14:1839-1850. 10.1093/hmg/ddi190, 15888477.
190. Kobayashi TT, Minowa OO, Sugitani YY, Takai SS, Mitani HH, Kobayashi EE, Noda TT, Hino OO. A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice. Proc Natl Acad Sci USA 2001, 98:8762-8767. 10.1073/pnas.151033798, 37509, 11438694.
191. Kobayashi T, Minowa O, Kuno J, Mitani H, Hino O, Noda T. Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. Cancer Res 1999, 59:1206-1211.
192. DiBella LM, Park A, Sun Z. Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway. Hum Mol Genet 2009, 18:595-606. 2722215, 19008302.
193. Yuan S, Li J, Diener DR, Choma MA, Rosenbaum JL, Sun Z. Target-of-rapamycin complex 1 (Torc1)-signaling modulates cilia size and function through protein synthesis regulation. Proc Natl Acad Sci 2012, 109:2021-2026. 10.1073/pnas.1112834109, 3277533, 22308353.
194. Lim DHK, Rehal PK, Nahorski MS, Macdonald F, Claessens T, van Geel M, Gijezen L, Gille JJP, Giraud S, Richard S, van Steensel M, Menko FH, Maher ER. A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene. Hum Mutat 2010, 31:E1043-E1051. 10.1002/humu.21130, 19802896.
195. Tee AR, Pause A. Birt-Hogg-Dubé: tumor suppressor function and signaling dynamics central to folliculin. Fam Cancer 2012, Epub ahead of print.
196. Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, Merino MJ. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol 2002, 26:1542-1552. 10.1097/00000478-200212000-00002, 12459621.
197. Baba M, Furihata M, Hong SB, Tessarollo L, Haines DC, Southon E, Patel V, Igarashi P, Alvord WG, Leighty R, Yao M, Bernardo M, Ileva L, Choyke P, Warren MB, Zbar B, Linehan WM, Schmidt LS. Kidney-targeted Birt-Hogg-Dubé gene inactivation in a mouse model: Erk1/2 and Akt-mTOR activation, cell hyperproliferation, and polycystic kidneys. JNCI 2008, 100:140-154. 10.1093/jnci/djm288, 2704336, 18182616.
198. Hasumi Y, Baba M, Ajima R, Hasumi H, Valera VA, Klein ME, Haines DC, Merino MJ, Hong S-B, Yamaguchi TP, Schmidt LS, Linehan WM. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci 2009, 106:18722-18727. 10.1073/pnas.0908853106, 2765925, 19850877.
199. Hartman TR, Nicolas E, Klein-Szanto A, Al-Saleem T, Cash TP, Simon MC, Henske EP. The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis. Oncogene 2009, 28:1594-1604. 10.1038/onc.2009.14, 2664853, 19234517.
200. Ollila S, Mäkelä TP. The tumor suppressor kinase LKB1: lessons from mouse models. J Mol Cell Biol 2011, 3:330-340. 10.1093/jmcb/mjr016, 21926085.
201. van der Velden YU, Wang L, Zevenhoven J, van Rooijen E, van Lohuizen M, Giles RH, Clevers H, Haramis A-PG. The serine-threonine kinase LKB1 is essential for survival under energetic stress in zebrafish. Proc Natl Acad Sci 2011, 108:4358-4363. 10.1073/pnas.1010210108, 3060253, 21368212.
202. Boehlke C, Kotsis F, Patel V, Braeg S, Voelker H, Bredt S, Beyer T, Janusch H, Hamann C, Gödel M, Müller K, Herbst M, Hornung M, Doerken M, Köttgen M, Nitschke R, Igarashi P, Walz G, Kuehn EW. Primary cilia regulate mTORC1 activity and cell size through Lkb1. Nat Cell Biol 2010, 12:1115-1122. 10.1038/ncb2117, 3390256, 20972424.
203. Wei C, Bhattaram VK, Igwe JC, Fleming E, Tirnauer JS. The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells. PLoS One 2012, 7:e41118. 10.1371/journal.pone.0041118, 3399794, 22815934.
204. Snape K, Hanks S, Ruark E, Barros-Núñez P, Elliott A, Murray A, Lane AH, Shannon N, Callier P, Chitayat D, Clayton-Smith J, FitzPatrick DR, Gisselsson D, Jacquemont S, Asakura-Hay K, Micale MA, Tolmie J, Turnpenny PD, Wright M, Douglas J, Rahman N. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet 2011, 43:527-529. 10.1038/ng.822, 3508359, 21552266.
205. Hanks S, Coleman K, Reid S, Plaja A, Firth H, FitzPatrick D, Kidd A, Méhes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 2004, 36:1159-1161. 10.1038/ng1449, 15475955.
206. Miyamoto T, Porazinski S, Wang H, Borovina A, Ciruna B, Shimizu A, Kajii T, Kikuchi A, Furutani-Seiki M, Matsuura S. Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates. Hum Mol Genet 2011, 20:2058-2070. 10.1093/hmg/ddr090, 21389084.
207. Suijkerbuijk SJE, van Osch MHJ, Bos FL, Hanks S, Rahman N, Kops GJPL. Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. Cancer Res 2010, 70:4891-4900. 10.1158/0008-5472.CAN-09-4319, 2887387, 20516114.
208. Parren LJMT, Frank J. Hereditary tumor syndromes featuring basal cell carcinomas. Br J Dermatol 2011, 165:30-34. 10.1111/j.1365-2133.2011.10334.x, 21428980.
209. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 2008, 8:743-754. 10.1038/nrc2503, 18813320.
210. Gómez García EB, Knoers NVAM. Gardner's syndrome (familial adenomatous polyposis): a cilia-related disorder. Lancet Oncol 2009, 10:727-735. 10.1016/S1470-2045(09)70167-6, 19573802.
211. Jimbo T, Kawasaki Y, Koyama R, Sato R, Takada S, Haraguchi K, Akiyama T. Identification of a link between the tumor suppressor APC and the kinesin superfamily. Nat Cell Biol 2002, 4:323-327. 10.1038/ncb779, 11912492.
212. Aoki K, Taketo MM. Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 2007, 120:3327-3335. 10.1242/jcs.03485, 17881494.
213. Jaulin F, Kreitzer G. KIF17 stabilizes microtubules and contributes to epithelial morphogenesis by acting at MT plus ends with EB1 and APC. J Cell Biol 2010, 190:443-460. 10.1083/jcb.201006044, 2922650, 20696710.
214. Moniz L, Dutt P, Haider N, Stambolic V. Nek family of kinases in cell cycle, checkpoint control and cancer. Cell Div 2011, 6:1-25. 10.1186/1747-1028-6-1, 3035582, 21255415.
215. Zalli D, Bayliss R, Fry AM. The Nek8 protein kinase, mutated in the human cystic kidney disease nephronophthisis, is both activated and degraded during ciliogenesis. Hum Mol Genet 2012, 21:1155-1171. 10.1093/hmg/ddr544, 3277313, 22106379.
216. Vogler C, Homan S, Pung A, Thorpe C, Barker J, Birkenmeier EH, Upadhya P. Clinical and pathologic findings in two new allelic murine models of polycystic kidney disease. J Am Soc Nephrol 1999, 10:2534-2539.
217. Mahjoub MR, Trapp ML, Quarmby LM. NIMA-related kinases defective in murine models of polycystic kidney diseases localize to primary cilia and centrosomes. J Am Soc Nephrol 2005, 16:3485-3489. 10.1681/ASN.2005080824, 16267153.
218. Thiel C, Kessler K, Giessl A, Dimmler A, Shalev SA, von der Haar S, Zenker M, Zahnleiter D, Stöss H, Beinder E, Abou Jamra R, Ekici AB, Schröder-Kreß N, Aigner T, Kirchner T, Reis A, Brandstätter JH, Rauch A. NEK1 mutations cause short-rib polydactyly syndrome type Majewski. Am J Hum Genet 2011, 88:106-114. 10.1016/j.ajhg.2010.12.004, 3014367, 21211617.
219. Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA. Centrosomes and cilia in human disease. Trends Genet 2011, 27:307-315. 10.1016/j.tig.2011.05.004, 3144269, 21680046.
220. Aboualaiwi WA, Ratnam S, Booth RL, Shah JV, Nauli SM. Endothelial cells from humans and mice with polycystic kidney disease are characterized by polyploidy and chromosome segregation defects through survivin down-regulation. Hum Mol Genet 2011, 20:354-367. 10.1093/hmg/ddq470, 3005905, 21041232.
221. Majumder S, Fisk HA. VDAC3 and Mps1 negatively regulate ciliogenesis. Cell Cycle 2013, 12:1-10. 10.4161/cc.23067, 3570496, 23255116.
222. Haraguchi K, Hayashi T, Jimbo T, Yamamoto T, Akiyama T. Role of the kinesin-2 family protein, KIF3, during mitosis. J Biol Chem 2006, 281:4094-4099. 10.1074/jbc.M507028200, 16298999.
223. Teng J, Rai T, Tanaka Y, Takei Y, Nakata T, Hirasawa M, Kulkarni AB, Hirokawa N. The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium. Nat Cell Biol 2005, 7:474-482. 10.1038/ncb1249, 15834408.
224. Sperka T, Wang J, Rudolph KL. DNA damage checkpoints in stem cells, ageing and cancer. Nat Rev Mol Cell Biol 2012, 13:579-590. 10.1038/nrm3420, 22914294.
225. Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong C-J, Hamilton BA, Červenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJF, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response-signaling. Cell 2012, 150:533-548. 10.1016/j.cell.2012.06.028, 3433835, 22863007.
226. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, Patil SB, Levy S, Ghosh AK, Murga-Zamalloa CA, van Reeuwijk J, Letteboer SJF, Sang L, Giles RH, Liu Q, Coene KLM, Estrada-Cuzcano A, Collin RWJ, McLaughlin HM, Held S, Kasanuki JM, Ramaswami G, Conte J, Lopez I, Washburn J, MacDonald J, Hu J, Yamashita Y, Maher ER, Guay-Woodford LM. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 2010, 42:840-850. 10.1038/ng.662, 2947620, 20835237.
227. Graser S, Stierhof Y-D, Lavoie SB, Gassner OS, Lamla S, Le Clech M, Nigg EA. Cep164, a novel centriole appendage protein required for primary cilium formation. J Cell Biol 2007, 179:321-330. 10.1083/jcb.200707181, 2064767, 17954613.
228. Saladino C, Bourke E, Conroy PC, Morrison CG. Centriole separation in DNA damage-induced centrosome amplification. Environ Mol Mutagen 2009, 50:725-732. 10.1002/em.20477, 19274769.
229. Conroy PC, Saladino C, Dantas TJ, Lalor P, Dockery P, Morrison CG. C-NAP1 and rootletin restrain DNA damage-induced centriole splitting and facilitate ciliogenesis. Cell Cycle 2012, 11:3769-3778. 10.4161/cc.21986, 23070519.
230. Christensen ST, Pedersen SF, Satir P, Veland IR, Schneider L. The primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair. Curr Top Dev Biol 2008, 85:261-301.
231. Jones TJ, Adapala RK, Geldenhuys WJ, Bursley C, Aboualaiwi WA, Nauli SM, Thodeti CK. Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of Hsp27 dependent actin cytoskeletal organization. J Cell Physiol 2012, 227:70-76. 10.1002/jcp.22704, 3202021, 21837772.
232. Simpson KJ, Selfors LM, Bui J, Reynolds A, Leake D, Khvorova A, Brugge JS. Identification of genes that regulate epithelial cell migration using an siRNA screening approach. Nat Cell Biol 2008, 10:1027-1038. 10.1038/ncb1762, 19160483.
233. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674. 10.1016/j.cell.2011.02.013, 21376230.
234. Zhang D, Sun L, Xian W, Liu F, Ling G, Xiao L, Liu Y, Peng Y, Haruna Y, Kanwar YS. Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity. Lab Invest 2010, 90:436-447. 10.1038/labinvest.2009.149, 20142807.