Compartments within a compartment: What C. elegans can tell us about ciliary subdomain composition, biogenesis, function, and disease

Organogenesis

Volumn 10, Issue 1, 2014, Pages 126-137

  Blacque, Oliver E ^a   Sanders, Anna Awm ^a  

^a UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

Basal body; Cilia; Ciliary tip; Ciliopathy; Diffusion barrier; Distal segment; Intraflagellar transport; Inversin compartment; Periciliary membrane; Transition zone

Indexed keywords

ARL13B PROTEIN; CLATHRIN; CNG 3 PROTEIN; CYCLIC NUCLEOTIDE GATED CHANNEL; DYNAMIN; KINESIN 2; NPHP2 PROTEIN; NPHP3 PROTEIN; NPHP9 PROTEIN; ORGANIC SOLUTE TRANSPORTER ANION; PROTEIN; RETINITIS PIGMENTOSA GENE 2; SIGNAL TRANSDUCING ADAPTOR PROTEIN; SONIC HEDGEHOG PROTEIN; TAX 2 PROTEIN; TAX 4 PROTEIN; TRANSLOCATING CHAIN ASSOCIATED MEMBRANE PROTEIN; UNCLASSIFIED DRUG;

ACTIVE TRANSPORT; AXONEME; BIOGENESIS; CAENORHABDITIS ELEGANS; CELL COMPARTMENTALIZATION; CELL MEMBRANE; CELL ORGANELLE; CELL POLARITY; CELL ULTRASTRUCTURE; CENTRIOLE; CENTROSOME; CHLAMYDOMONAS; DENDRITE; DIFFUSION; ENDOCYTOSIS; EUKARYOTIC FLAGELLUM; INTRACELLULAR SIGNALING; JOUBERT SYNDROME; KINETOSOME; LIPID COMPOSITION; MECKEL SYNDROME; MICROTUBULE; MICROTUBULE ASSEMBLY; NEPHRONOPHTHISIS; NONHUMAN; PERICILIARY MEMBRANE COMPARTMENT; PLANAR CELL POLARITY; PROTEIN LOCALIZATION; REVIEW; SENSORY NERVE CELL; SPINDLE POLE; ANIMAL; CYTOLOGY; DISEASE MODEL; HUMAN; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; BIOGENESIS; CAENORHABDITIS ELEGANS; CILIA; DISEASE MODELS, ANIMAL; HUMANS; SIGNAL TRANSDUCTION;

EID: 84901401668     PISSN: 15476278     EISSN: 15558592     Source Type: Journal    
DOI: 10.4161/org.28830     Document Type: Review

References (138)

1. van Dam TJ, Wheway G, Slaats GG, Huynen MA, Giles RH; SYSCILIA Study Group. The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium. Cilia 2013; 2:7; PMID:23725226; http://dx.doi.org/10.1186/2046-2530-2-7
2. Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 2011; 26:1039-56; PMID:21210154; http://dx.doi.org/10.1007/ s00467-010-1731-7
3. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 2010; 11:331-44; PMID:20395968; http://dx.doi.org/10.1038/nrg2774
4. Goggolidou P. Wnt and planar cell polarity signaling in cystic renal disease. Organogenesis 2013; 10:10; PMID:24162855
5. Christensen ST, Clement CA, Satir P, Pedersen LB. Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling. J Pathol 2012; 226:172-84; PMID:21956154; http://dx.doi.org/10.1002/path.3004
6. Seeger-Nukpezah T, Golemis EA. The extracellular matrix and ciliary signaling. Curr Opin Cell Biol 2012; 24:652-61; PMID:22819513; http://dx.doi.org/10.1016/j.ceb.2012.06.002
7. 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; 145:1129-41; PMID:21703454; http://dx.doi.org/10.1016/j. cell.2011.05.030
8. Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, et al. Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet 2009; 41:1032-6; PMID:19668216; http://dx.doi.org/10.1038/ng.423
9. Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, Christensen ST. PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol 2005; 15:1861-6; PMID:16243034; http://dx.doi.org/10.1016/j.cub.2005.09.012
10. Reiter JF, Blacque OE, Leroux MR. The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep 2012; 13:608-18; PMID:22653444; http://dx.doi.org/10.1038/embor.2012.73
11. Shiba D, Yamaoka Y, Hagiwara H, Takamatsu T, Hamada H, Yokoyama T. Localization of Inv in a distinctive intraciliary compartment requires the C-terminal ninein-homolog-containing region. J Cell Sci 2009; 122:44-54; PMID:19050042; http://dx.doi.org/10.1242/jcs.037408
12. Chih B, Liu P, Chinn Y, Chalouni C, Komuves LG, Hass PE, Sandoval W, Peterson AS. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nat Cell Biol 2012; 14:61-72; PMID:22179047; http://dx.doi.org/10.1038/ncb2410
13. Craige B, Tsao CC, Diener DR, Hou Y, Lechtreck KF, Rosenbaum JL, Witman GB. CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content. J Cell Biol 2010; 190:927-40; PMID:20819941; http://dx.doi.org/10.1083/jcb.201006105
14. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, et al. A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 2011; 43:776-84; PMID:21725307; http://dx.doi.org/10.1038/ng.891
15. Williams CL, Li C, Kida K, Inglis PN, Mohan S, Semenec L, Bialas NJ, Stupay RM, Chen N, Blacque OE, et al. MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J Cell Biol 2011; 192:1023-41; PMID:21422230; http://dx.doi.org/10.1083/jcb.201012116
16. 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 2010; 329:436-9; PMID:20558667; http://dx.doi.org/10.1126/science.1191054
17. Kee HL, Dishinger JF, Blasius TL, 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; 14:431-7; PMID:22388888; http://dx.doi.org/10.1038/ncb2450
18. Hsiao Y-C, Tuz K, Ferland RJ. Trafficking in and to the primary cilium. Cilia 2012; 1:4; PMID:23351793; http://dx.doi.org/10.1186/2046-2530-1-4
19. Blacque OE, Cevik S, Kaplan OI. Intraflagellar transport: from molecular characterisation to mechanism. Front Biosci 2008; 13:2633-52; PMID:17981739; http://dx.doi.org/10.2741/2871
20. Ishikawa H, Marshall WF. Ciliogenesis: building the cell's antenna. Nat Rev Mol Cell Biol 2011; 12:222-34; PMID:21427764; http://dx.doi.org/10.1038/ nrm3085
21. Bae YK, Qin H, Knobel KM, Hu J, Rosenbaum JL, Barr MM. General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia. Development 2006; 133:3859-70; PMID:16943275; http://dx.doi.org/10.1242/dev.02555
22. Deretic D, Huber LA, Ransom N, Mancini M, Simons K, Papermaster DS. rab8 in retinal photoreceptors may participate in rhodopsin transport and in rod outer segment disk morphogenesis. J Cell Sci 1995; 108:215-24; PMID:7738098
23. Dwyer ND, Adler CE, Crump JG, L'Etoile ND, Bargmann CI. Polarized dendritic transport and the AP-1 mu1 clathrin adaptor UNC-101 localize odorant receptors to olfactory cilia. Neuron 2001; 31:277-87; PMID:11502258; http://dx.doi.org/10.1016/S0896-6273(01)00361-0
24. Kaplan OI, Doroquez DB, Cevik S, Bowie RV, Clarke L, Sanders AA, Kida K, Rappoport JZ, Sengupta P, Blacque OE. Endocytosis genes facilitate protein and membrane transport in C. elegans sensory cilia. Curr Biol 2012; 22:451-60; PMID:22342749; http://dx.doi.org/10.1016/j.cub.2012.01.060
25. Kaplan OI, Molla-Herman A, Cevik S, Ghossoub R, Kida K, Kimura Y, Jenkins P, Martens JR, Setou M, Benmerah A, et al. The AP-1 clathrin adaptor facilitates cilium formation and functions with RAB-8 in C. elegans ciliary membrane transport. J Cell Sci 2010; 123:3966-77; PMID:20980383; http://dx.doi.org/10.1242/jcs.073908
26. Mazelova J, Astuto-Gribble L, Inoue H, Tam BM, Schonteich E, Prekeris R, Moritz OL, Randazzo PA, Deretic D. Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4. EMBO J 2009; 28:183-92; PMID:19153612; http://dx.doi.org/10.1038/emboj.2008.267
27. Molla-Herman A, Ghossoub R, Blisnick T, Meunier A, Serres C, Silbermann F, Emmerson C, Romeo K, Bourdoncle P, Schmitt A, et al. The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia. J Cell Sci 2010; 123:1785-95; PMID:20427320; http://dx.doi.org/10.1242/jcs.059519
28. Moritz OL, Tam BM, Hurd LL, Peränen J, Deretic D, Papermaster DS. Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death of transgenic Xenopus rods. Mol Biol Cell 2001; 12:2341-51; PMID:11514620; http://dx.doi.org/10.1091/mbc.12.8.2341
29. Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peränen J, Merdes A, Slusarski DC, Scheller RH, Bazan JF, Sheffield VC, et al. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 2007; 129:1201-13; PMID:17574030; http://dx.doi.org/10.1016/j.cell.2007. 03.053
30. Nachury MV, Seeley ES, Jin H. Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier? Annu Rev Cell Dev Biol 2010; 26:59-87; PMID:19575670; http://dx.doi.org/10.1146/annurev.cellbio.042308.113337
31. Westlake CJ, Baye LM, Nachury MV, Wright KJ, Ervin KE, Phu L, Chalouni C, Beck JS, Kirkpatrick DS, Slusarski DC, et al. 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 U S A 2011; 108:2759-64; PMID:21273506; http://dx.doi.org/10.1073/pnas.1018823108
32. Zuo X, Guo W, Lipschutz JH. The exocyst protein Sec10 is necessary for primary ciliogenesis and cystogenesis in vitro. Mol Biol Cell 2009; 20:2522-9; PMID:19297529; http://dx.doi.org/10.1091/mbc.E08-07-0772
33. Clement CA, Ajbro KD, Koefoed K, Vestergaard ML, Veland IR, Henriques de Jesus MP, Pedersen LB, Benmerah A, Andersen CY, Larsen LA, et al. TGF-β signaling is associated with endocytosis at the pocket region of the primary cilium. Cell Rep 2013; 3:1806-14; PMID:23746451; http://dx.doi.org/10.1016/j. celrep.2013.05.020
34. Dishinger JF, Kee HL, Jenkins PM, Fan S, Hurd TW, Hammond JW, Truong YN, 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; 12:703-10; PMID:20526328; http://dx.doi.org/10.1038/ncb2073
35. Fan S, Fogg V, Wang Q, Chen XW, Liu CJ, Margolis B. A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin beta interactions. J Cell Biol 2007; 178:387-98; PMID:17646395; http://dx.doi.org/10.1083/jcb. 200609096
36. Fan S, Whiteman EL, Hurd TW, McIntyre JC, Dishinger JF, Liu CJ, Martens JR, Verhey KJ, Sajjan U, Margolis B. Induction of Ran GTP drives ciliogenesis. Mol Biol Cell 2011; 22:4539-48; PMID:21998203; http://dx.doi.org/10.1091/mbc. E11-03-0267
37. Hurd TW, Fan S, Margolis BL. Localization of retinitis pigmentosa 2 to cilia is regulated by Importin beta2. J Cell Sci 2011; 124:718-26; PMID:21285245; http://dx.doi.org/10.1242/jcs.070839
38. Breslow DK, Koslover EF, Seydel F, Spakowitz AJ, Nachury MV. An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier. J Cell Biol 2013; 203:129-47; PMID:24100294; http://dx.doi.org/10.1083/ jcb.201212024
39. Belzile O, Hernandez-Lara CI, Wang Q, Snell WJ. Regulated membrane protein entry into flagella is facilitated by cytoplasmic microtubules and does not require IFT. Curr Biol 2013; 23:1460-5; PMID:23891117; http://dx.doi.org/10. 1016/j.cub.2013.06.025
40. Kim S, Dynlacht BD. Assembling a primary cilium. Curr Opin Cell Biol 2013; 25:506-11; PMID:23747070; http://dx.doi.org/10.1016/j.ceb.2013.04.011
41. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002; 3:813-25; PMID:12415299; http://dx.doi.org/10.1038/nrm952
42. Melkonian M. The functional analysis of the flagellar apparatus in green algae. Symp Soc Exp Biol 1982; 35:589-606; PMID:6764051
43. Weiss RL, Goodenough DA, Goodenough UW. Membrane particle arrays associated with the basal body and with contractile vacuole secretion in Chlamydomonas. J Cell Biol 1977; 72:133-43; PMID:830652; http://dx.doi.org/10. 1083/jcb.72.1.133
44. 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; 11:1586-90; PMID:11676918; http://dx.doi.org/10.1016/S0960-9822(01)00484-5
45. Bornens M. Centrosome composition and microtubule anchoring mechanisms. Curr Opin Cell Biol 2002; 14:25-34; PMID:11792541; http://dx.doi.org/10.1016/ S0955-0674(01)00290-3
46. Kobayashi T, Dynlacht BD. Regulating the transition from centriole to basal body. J Cell Biol 2011; 193:435-44; PMID:21536747; http://dx.doi.org/10. 1083/jcb.201101005
47. Czarnecki PG, Shah JV. The ciliary transition zone: from morphology and molecules to medicine. Trends Cell Biol 2012; 22:201-10; PMID:22401885; http://dx.doi.org/10.1016/j.tcb.2012.02.001
48. Cevik S, Sanders AA, Van Wijk E, Boldt K, Clarke L, van Reeuwijk J, Hori Y, Horn N, Hetterschijt L, Wdowicz A, et al. Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain. PLoS Genet 2013; 9:e1003977; PMID:24339792; http://dx.doi.org/10.1371/journal.pgen.1003977
49. Gilula NB, Satir P. The ciliary necklace. A ciliary membrane specialization. J Cell Biol 1972; 53:494-509; PMID:4554367; http://dx.doi.org/ 10.1083/jcb.53.2.494
50. Inglis PN, Ou G, Leroux MR, Scholey JM. The sensory cilia of C. elegans (March 8, 2007). WormBook, ed The C elegans Research Community, WormBook, doi/101895/wormbook11231 2007.
51. Reese TS. Olfactory Cilia in the Frog. J Cell Biol 1965; 25:209-30; PMID:19866665; http://dx.doi.org/10.1083/jcb.25.2.209
52. Hidaka K, Ashizawa N, Endoh H, Watanabe M, Fukumoto S. Fine structure of the cilia in the pancreatic duct of WBN/Kob rat. Int J Pancreatol 1995; 18:207-13; PMID:8708391
53. Mesland DA, Hoffman JL, Caligor E, Goodenough UW. Flagellar tip activation stimulated by membrane adhesions in Chlamydomonas gametes. J Cell Biol 1980; 84:599-617; PMID:7358792; http://dx.doi.org/10.1083/jcb.84.3.599
54. Webber WA, Lee J. Fine structure of mammalian renal cilia. Anat Rec 1975; 182:339-43; PMID:1155803; http://dx.doi.org/10.1002/ar.1091820307
55. Shiba D, Manning DK, Koga H, Beier DR, Yokoyama T. Inv acts as a molecular anchor for Nphp3 and Nek8 in the proximal segment of primary cilia. Cytoskeleton (Hoboken) 2010; 67:112-9; PMID:20169535
56. Haycraft CJ, Banizs B, Aydin-Son Y, Zhang Q, Michaud EJ, Yoder BK. Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet 2005; 1:e53; PMID:16254602; http://dx.doi.org/10.1371/ journal.pgen.0010053
57. Flannery RJ, French DA, Kleene SJ. Clustering of cyclic-nucleotide-gated channels in olfactory cilia. Biophys J 2006; 91:179-88; PMID:16603488; http://dx.doi.org/10.1529/biophysj.105.079046
58. Matsuzaki O, Bakin RE, Cai X, Menco BP, Ronnett GV. Localization of the olfactory cyclic nucleotide-gated channel subunit 1 in normal, embryonic and regenerating olfactory epithelium. Neuroscience 1999; 94:131-40; PMID:10613503; http://dx.doi.org/10.1016/S0306-4522(99)00228-6
59. Broekhuis JR, Leong WY, Jansen G. Regulation of cilium length and intraflagellar transport. Int Rev Cell Mol Biol 2013; 303:101-38; PMID:23445809; http://dx.doi.org/10.1016/B978-0-12-407697-6.00003-9
60. Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, et al. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev 2004; 18:1630-42; PMID:15231740; http://dx.doi.org/10.1101/ gad.1194004
61. Cevik S, Hori Y, Kaplan OI, Kida K, Toivenon T, Foley-Fisher C, Cottell D, Katada T, Kontani K, Blacque OE. Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans. J Cell Biol 2010; 188:953-69; PMID:20231383; http://dx.doi.org/10.1083/jcb.200908133
62. Li Y, Wei Q, Zhang Y, Ling K, Hu J. The small GTPases ARL-13 and ARL-3 coordinate intraflagellar transport and ciliogenesis. J Cell Biol 2010; 189:1039-51; PMID:20530210; http://dx.doi.org/10.1083/jcb.200912001
63. Ou G, Blacque OE, Snow JJ, Leroux MR, Scholey JM. Functional coordination of intraflagellar transport motors. Nature 2005; 436:583-7; PMID:16049494; http://dx.doi.org/10.1038/nature03818
64. Wei Q, Zhang Y, Li Y, Zhang Q, Ling K, Hu J. The BBSome controls IFT assembly and turnaround in cilia. Nat Cell Biol 2012; 14:950-7; PMID:22922713; http://dx.doi.org/10.1038/ncb2560
65. Broekhuis JR, Rademakers S, Burghoorn J, Jansen G. SQL-1, homologue of the Golgi protein GMAP210, modulates intraflagellar transport in C. elegans. J Cell Sci 2013; 126:1785-95; PMID:23444385; http://dx.doi.org/10.1242/jcs.116640
66. Olivier-Mason A, Wojtyniak M, Bowie RV, Nechipurenko IV, Blacque OE, Sengupta P. Transmembrane protein OSTA-1 shapes sensory cilia morphology via regulation of intracellular membrane trafficking in C. elegans. Development 2013; 140:1560-72; PMID:23482491; http://dx.doi.org/10.1242/dev.086249
67. Hu J, Wittekind SG, Barr MM. STAM and Hrs down-regulate ciliary TRP receptors. Mol Biol Cell 2007; 18:3277-89; PMID:17581863; http://dx.doi.org/10. 1091/mbc.E07-03-0239
68. Blacque OE, Li C, Inglis PN, Esmail MA, Ou G, Mah AK, Baillie DL, Scholey JM, Leroux MR. The WD repeat-containing protein IFTA-1 is required for retrograde intraflagellar transport. Mol Biol Cell 2006; 17:5053-62; PMID:17021254; http://dx.doi.org/10.1091/mbc.E06-06-0571
69. Blacque OE, Perens EA, Boroevich KA, Inglis PN, Li C, Warner A, Khattra J, Holt RA, Ou G, Mah AK, et al. Functional genomics of the cilium, a sensory organelle. Curr Biol 2005; 15:935-41; PMID:15916950; http://dx.doi.org/10.1016/ j.cub.2005.04.059
70. Efimenko E, Blacque OE, Ou G, Haycraft CJ, Yoder BK, Scholey JM, Leroux MR, Swoboda P. Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory cilia. Mol Biol Cell 2006; 17:4801-11; PMID:16957054; http://dx.doi.org/10.1091/mbc.E06-04-0260
71. Bacaj T, Lu Y, Shaham S. The conserved proteins CHE-12 and DYF-11 are required for sensory cilium function in Caenorhabditis elegans. Genetics 2008; 178:989-1002; PMID:18245347; http://dx.doi.org/10.1534/genetics.107.082453
72. Li C, Inglis PN, Leitch CC, Efimenko E, Zaghloul NA, Mok CA, Davis EE, Bialas NJ, Healey MP, Héon E, et al. An essential role for DYF-11/MIPT3 in assembling functional intraflagellar transport complexes. PLoS Genet 2008; 4:e1000044; PMID:18369462; http://dx.doi.org/10.1371/journal.pgen.1000044
73. Doroquez DB, Berciu C, Anderson JR, Sengupta P, Nicastro D. A high-resolution morphological and ultrastructural map of anterior sensory cilia and glia in Caenorhabditis elegans. Elife 2014; 3:e01948; PMID:24668170; http://dx.doi.org/10.7554/eLife.01948
74. Perkins LA, Hedgecock EM, Thomson JN, Culotti JG. Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol 1986; 117:456-87; PMID:2428682; http://dx.doi.org/10.1016/0012-1606(86)90314-3
75. Manandhar G, Simerly C, Salisbury JL, Schatten G. Centriole and centrin degeneration during mouse spermiogenesis. Cell Motil Cytoskeleton 1999; 43:137-44; PMID:10379838; http://dx.doi.org/10.1002/(SICI)1097-0169 (1999)43:2〈137::AIDCM5〉3.0.CO;2-7
76. Manandhar G, Simerly C, Schatten G. Highly degenerated distal centrioles in rhesus and human spermatozoa. Hum Reprod 2000; 15:256-63; PMID:10655294; http://dx.doi.org/10.1093/humrep/15.2.256
77. Dammermann A, Pemble H, Mitchell BJ, McLeod I, Yates JR 3rd, Kintner C, Desai AB, Oegema K. The hydrolethalus syndrome protein HYLS-1 links core centriole structure to cilia formation. Genes Dev 2009; 23:2046-59; PMID:19656802; http://dx.doi.org/10.1101/gad.1810409
78. Mohan S, Timbers TA, Kennedy J, Blacque OE, Leroux MR. Striated rootlet and nonfilamentous forms of rootletin maintain ciliary function. Curr Biol 2013; 23:2016-22; PMID:24094853; http://dx.doi.org/10.1016/j.cub.2013.08.033
79. Wei Q, Xu Q, Zhang Y, Li Y, Zhang Q, Hu Z, Harris PC, Torres VE, Ling K, Hu J. Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes. Nat Commun 2013; 4:2750; PMID:24231678; http://dx.doi.org/10.1038/ncomms3750
80. Yang J, Gao J, Adamian M, Wen XH, Pawlyk B, Zhang L, Sanderson MJ, Zuo J, Makino CL, Li T. The ciliary rootlet maintains long-term stability of sensory cilia. Mol Cell Biol 2005; 25:4129-37; PMID:15870283; http://dx.doi.org/10.1128/ MCB.25.10.4129-4137.2005
81. Wang J, Silva M, Haas LA, Morsci NS, Nguyen KC, Hall DH, Barr MM. C. elegans Ciliated Sensory Neurons Release Extracellular Vesicles that Function in Animal Communication. Curr Biol 2014; 24:519-25; PMID:24530063; http://dx.doi.org/10.1016/j.cub.2014.01.002
82. Wood CR, Huang K, Diener DR, Rosenbaum JL. The cilium secretes bioactive ectosomes. Curr Biol 2013; 23:906-11; PMID:23623554; http://dx.doi.org/10.1016/ j.cub.2013.04.019
83. Allen CL, Goulding D, Field MC. Clathrin-mediated endocytosis is essential in Trypanosoma brucei. EMBO J 2003; 22:4991-5002; PMID:14517238; http://dx.doi.org/10.1093/emboj/cdg481
84. Evans RJ, Schwarz N, Nagel-Wolfrum K, Wolfrum U, Hardcastle AJ, Cheetham ME. The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium. Hum Mol Genet 2010; 19:1358-67; PMID:20106869; http://dx.doi.org/10.1093/hmg/ddq012
85. Stephan A, Vaughan S, Shaw MK, Gull K, McKean PG. An essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport. Traffic 2007; 8:1323-30; PMID:17645436; http://dx.doi.org/10.1111/j. 1600-0854.2007.00611.x
86. Stefan CJ, Manford AG, Emr SD. ER-PM connections: sites of information transfer and inter-organelle communication. Curr Opin Cell Biol 2013; 25:434-42; PMID:23522446; http://dx.doi.org/10.1016/j.ceb.2013.02.020
87. Lebiedzinska M, Szabadkai G, Jones AW, Duszynski J, Wieckowski MR. Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles. Int J Biochem Cell Biol 2009; 41:1805-16; PMID:19703651; http://dx.doi.org/10.1016/j.biocel.2009.02.017
88. Ramírez OA, Couve A. The endoplasmic reticulum and protein trafficking in dendrites and axons. Trends Cell Biol 2011; 21:219-27; PMID:21215635; http://dx.doi.org/10.1016/j.tcb.2010.12.003
89. Francis SS, Sfakianos J, Lo B, Mellman I. A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells. J Cell Biol 2011; 193:219-33; PMID:21444686; http://dx.doi.org/10.1083/jcb.201009001
90. Huang L, Szymanska K, Jensen VL, Janecke AR, Innes AM, Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, et al. 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; 89:713-30; PMID:22152675; http://dx.doi.org/10.1016/j.ajhg.2011.11.005
91. Bialas NJ, Inglis PN, Li C, Robinson JF, Parker JD, Healey MP, Davis EE, Inglis CD, Toivonen T, Cottell DC, et al. Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins. J Cell Sci 2009; 122:611-24; PMID:19208769; http://dx.doi.org/10.1242/jcs.028621
92. Williams CL, Winkelbauer ME, Schafer JC, Michaud EJ, Yoder BK. Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis elegans ciliogenesis. Mol Biol Cell 2008; 19:2154-68; PMID:18337471; http://dx.doi.org/10.1091/mbc.E07-10-1070
93. Jauregui AR, Nguyen KC, Hall DH, Barr MM. The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure. J Cell Biol 2008; 180:973-88; PMID:18316409; http://dx.doi.org/10.1083/jcb.200707090
94. Heiman MG, Shaham S. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell 2009; 137:344-55; PMID:19344940; http://dx.doi.org/10.1016/j.cell.2009.01.057
95. Williams CL, Masyukova SV, Yoder BK. Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS-3 and NPHP-4. J Am Soc Nephrol 2010; 21:782-93; PMID:20150540; http://dx.doi.org/10.1681/ASN.2009060597
96. Garcia-Gonzalo FR, Reiter JF. Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J Cell Biol 2012; 197:697-709; PMID:22689651; http://dx.doi.org/10.1083/jcb.201111146
97. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 2011; 145:513-28; PMID:21565611; http://dx.doi.org/10.1016/j.cell.2011.04.019
98. Mukhopadhyay S, Lu Y, Qin H, Lanjuin A, Shaham S, Sengupta P. Distinct IFT mechanisms contribute to the generation of ciliary structural diversity in C. elegans. EMBO J 2007; 26:2966-80; PMID:17510633; http://dx.doi.org/10.1038/ sj.emboj.7601717
99. Snow JJ, Ou G, Gunnarson AL, Walker MR, Zhou HM, Brust-Mascher I, Scholey JM. Two anterograde intraflagellar transport motors cooperate to build sensory cilia on C. elegans neurons. Nat Cell Biol 2004; 6:1109-13; PMID:15489852; http://dx.doi.org/10.1038/ncb1186
100. Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, Boehlke C, Schell C, Yasunaga T, Helmstädter M, et al. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet 2013; 45:951-6; PMID:23793029; http://dx.doi.org/10.1038/ng.2681
101. Larkins CE, Aviles GD, East MP, Kahn RA, Caspary T. Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins. Mol Biol Cell 2011; 22:4694-703; PMID:21976698; http://dx.doi.org/10.1091/mbc.E10-12-0994
102. Warburton-Pitt SR, Jauregui AR, Li C, Wang J, Leroux MR, Barr MM. Ciliogenesis in Caenorhabditis elegans requires genetic interactions between ciliary middle segment localized NPHP-2 (inversin) and transition zone-associated proteins. J Cell Sci 2012; 125:2592-603; PMID:22393243; http://dx.doi.org/10.1242/jcs.095539
103. Mukhopadhyay S, Lu Y, Shaham S, Sengupta P. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans. Dev Cell 2008; 14:762-74; PMID:18477458; http://dx.doi.org/10.1016/j.devcel.2008.03.002
104. Wojtyniak M, Brear AG, O'Halloran DM, Sengupta P. Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization in C. elegans. J Cell Sci 2013; 126:4381-95; PMID:23886944; http://dx.doi.org/ 10.1242/jcs.127274
105. Caspary T, Larkins CE, Anderson KV. The graded response to Sonic Hedgehog depends on cilia architecture. Dev Cell 2007; 12:767-78; PMID:17488627; http://dx.doi.org/10.1016/j.devcel.2007.03.004
106. Duldulao NA, Lee S, Sun Z. Cilia localization is essential for in vivo functions of the Joubert syndrome protein Arl13b/Scorpion. Development 2009; 136:4033-42; PMID:19906870; http://dx.doi.org/10.1242/dev.036350
107. Tyler KM, Fridberg A, Toriello KM, Olson CL, Cieslak JA, Hazlett TL, Engman DM. Flagellar membrane localization via association with lipid rafts. J Cell Sci 2009; 122:859-66; PMID:19240119; http://dx.doi.org/10.1242/jcs.037721
108. Nakata K, Shiba D, Kobayashi D, Yokoyama T. Targeting of Nphp3 to the primary cilia is controlled by an N-terminal myristoylation site and coiled-coil domains. Cytoskeleton (Hoboken) 2012; 69:221-34; PMID:22328406; http://dx.doi.org/10.1002/cm.21014
109. Emmer BT, Souther C, Toriello KM, Olson CL, Epting CL, Engman DM. Identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane. J Cell Sci 2009; 122:867-74; PMID:19240115; http://dx.doi.org/10.1242/jcs.041764
110. Wright KJ, Baye LM, Olivier-Mason A, Mukhopadhyay S, Sang L, Kwong M, Wang W, Pretorius PR, Sheffield VC, Sengupta P, et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev 2011; 25:2347-60; PMID:22085962; http://dx.doi.org/10.1101/gad.173443.111
111. Chailley B, Bork K, Gounon P, Sandoz D. Immunological detection of actin in isolated cilia from quail oviduct. Biol Cell 1986; 58:43-52; PMID:2952200; http://dx.doi.org/10.1111/j.1768-322X.1986.tb00487.x
112. Habbig S, Bartram MP, Sägmüller JG, Griessmann A, Franke M, Müller RU, Schwarz R, Hoehne M, Bergmann C, Tessmer C, et al. The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ. Hum Mol Genet 2012; 21:5528-38; PMID:23026745; http://dx.doi.org/10.1093/hmg/dds408
113. Morgan D, Eley L, Sayer J, Strachan T, Yates LM, Craighead AS, Goodship JA. Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle. Hum Mol Genet 2002; 11:3345-50; PMID:12471060; http://dx.doi.org/ 10.1093/hmg/11.26.3345
114. 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; 21:1155-71; PMID:22106379; http://dx.doi.org/10.1093/hmg/ddr544
115. Higginbotham H, Eom TY, Mariani LE, Bachleda A, Hirt J, Gukassyan V, Cusack CL, Lai C, Caspary T, Anton ES. Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex. Dev Cell 2012; 23:925-38; PMID:23153492; http://dx.doi.org/10.1016/j.devcel.2012.09. 019
116. Higginbotham H, Guo J, Yokota Y, Umberger NL, Su CY, Li J, Verma N, Hirt J, Ghukasyan V, Caspary T, et al. Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation. Nat Neurosci 2013; 16:1000-7; PMID:23817546; http://dx.doi.org/10.1038/nn.3451
117. Mahuzier A, Gaudé HM, Grampa V, Anselme I, Silbermann F, Leroux-Berger M, Delacour D, Ezan J, Montcouquiol M, Saunier S, et al. Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity. J Cell Biol 2012; 198:927-40; PMID:22927466; http://dx.doi.org/10.1083/jcb.201111009
118. Zhao C, Malicki J. Nephrocystins and MKS proteins interact with IFT particle and facilitate transport of selected ciliary cargos. EMBO J 2011; 30:2532-44; PMID:21602787; http://dx.doi.org/10.1038/emboj.2011.165
119. Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Krönig C, Schermer B, Benzing T, Cabello OA, Jenny A, et al. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 2005; 37:537-43; PMID:15852005; http://dx.doi.org/10.1038/ng1552
120. Lienkamp S, Ganner A, Boehlke C, Schmidt T, Arnold SJ, Schäfer T, Romaker D, Schuler J, Hoff S, Powelske C, et al. Inversin relays Frizzled-8 signals to promote proximal pronephros development. Proc Natl Acad Sci U S A 2010; 107:20388-93; PMID:21059920; http://dx.doi.org/10.1073/pnas.1013070107
121. Veland IR, Montjean R, Eley L, Pedersen LB, Schwab A, Goodship J, Kristiansen K, Pedersen SF, Saunier S, Christensen ST. Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration. PLoS One 2013; 8:e60193; PMID:23593172; http://dx.doi.org/10.1371/journal.pone.0060193
122. Choi HJ, Lin JR, Vannier JB, Slaats GG, Kile AC, Paulsen RD, Manning DK, Beier DR, Giles RH, Boulton SJ, et al. NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies. Mol Cell 2013; 51:423-39; PMID:23973373; http://dx.doi.org/10.1016/j.molcel.2013.08.006
123. Trapp ML, Galtseva A, Manning DK, Beier DR, Rosenblum ND, Quarmby LM. Defects in ciliary localization of Nek8 is associated with cystogenesis. Pediatr Nephrol 2008; 23:377-87; PMID:18189147; http://dx.doi.org/10.1007/s00467-007- 0692-y
124. Burghoorn J, Dekkers MP, Rademakers S, de Jong T, Willemsen R, Jansen G. Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans. Proc Natl Acad Sci U S A 2007; 104:7157-62; PMID:17420466; http://dx.doi.org/10.1073/ pnas.0606974104
125. Hao L, Thein M, Brust-Mascher I, Civelekoglu-Scholey G, Lu Y, Acar S, Prevo B, Shaham S, Scholey JM. Intraflagellar transport delivers tubulin isotypes to sensory cilium middle and distal segments. Nat Cell Biol 2011; 13:790-8; PMID:21642982; http://dx.doi.org/10.1038/ncb2268
126. Ou G, Koga M, Blacque OE, Murayama T, Ohshima Y, Schafer JC, Li C, Yoder BK, Leroux MR, Scholey JM. Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles. Mol Biol Cell 2007; 18:1554-69; PMID:17314406; http://dx.doi.org/10.1091/mbc.E06-09-0805
127. Gray RS, Abitua PB, Wlodarczyk BJ, Szabo-Rogers HL, Blanchard O, Lee I, Weiss GS, Liu KJ, Marcotte EM, Wallingford JB, et al. The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development. Nat Cell Biol 2009; 11:1225-32; PMID:19767740; http://dx.doi.org/10.1038/ncb1966
128. Pedersen LB, Rosenbaum JL. Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr Top Dev Biol 2008; 85:23-61; PMID:19147001; http://dx.doi.org/10.1016/S0070-2153(08)00802-8
129. Schrøder JM, Larsen J, Komarova Y, Akhmanova A, Thorsteinsson RI, Grigoriev I, Manguso R, Christensen ST, Pedersen SF, Geimer S, et al. EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. J Cell Sci 2011; 124:2539-51; PMID:21768326; http://dx.doi.org/10.1242/jcs.085852
130. Pedersen LB, Geimer S, Sloboda RD, Rosenbaum JL. The Microtubule plus end-tracking protein EB1 is localized to the flagellar tip and basal bodies in Chlamydomonas reinhardtii. Curr Biol 2003; 13:1969-74; PMID:14614822; http://dx.doi.org/10.1016/j.cub.2003.10.058
131. Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 2013; 14:416-29; PMID:23719536; http://dx.doi.org/10.1038/nrm3598
132. Lee J, Moon S, Cha Y, Chung YD. Drosophila TRPN(=NOMPC) channel localizes to the distal end of mechanosensory cilia. PLoS One 2010; 5:e11012; PMID:20543979; http://dx.doi.org/10.1371/journal.pone.0011012
133. Brooks ER, Wallingford JB. Control of vertebrate intraflagellar transport by the planar cell polarity effector Fuz. J Cell Biol 2012; 198:37-45; PMID:22778277; http://dx.doi.org/10.1083/jcb.201204072
134. Pedersen LB, Geimer S, Rosenbaum JL. Dissecting the molecular mechanisms of intraflagellar transport in chlamydomonas. Curr Biol 2006; 16:450-9; PMID:16527740; http://dx.doi.org/10.1016/j.cub.2006.02.020
135. Johnson KA, Rosenbaum JL. Polarity of flagellar assembly in Chlamydomonas. J Cell Biol 1992; 119:1605-11; PMID:1281816; http://dx.doi.org/ 10.1083/jcb.119.6.1605
136. Wren KN, Craft JM, Tritschler D, Schauer A, Patel DK, Smith EF, Porter ME, Kner P, Lechtreck KF. A differential cargo-loading model of ciliary length regulation by IFT. Curr Biol 2013; 23:2463-71; PMID:24316207; http://dx.doi.org/10.1016/j.cub.2013.10.044
137. Pedersen LB, Miller MS, Geimer S, Leitch JM, Rosenbaum JL, Cole DG. Chlamydomonas IFT172 is encoded by FLA11, interacts with CrEB1, and regulates IFT at the flagellar tip. Curr Biol 2005; 15:262-6; PMID:15694311; http://dx.doi.org/10.1016/j.cub.2005.01.037
138. Young RW. The renewal of rod and cone outer segments in the rhesus monkey. J Cell Biol 1971; 49:303-18; PMID:19866760; http://dx.doi.org/10.1083/ jcb.49.2.303