Formation of the transition zone by Mks5/Rpgrip1L establishes a ciliary zone of exclusion (CIZE) that compartmentalises ciliary signalling proteins and controls PIP2 ciliary abundance

EMBO Journal

Volumn 34, Issue 20, 2015, Pages 2537-2556

  Jensen, Victor L ^a   Li, Chunmei ^a   Bowie, Rachel V ^b   Clarke, Lara ^b   Mohan, Swetha ^a   Blacque, Oliver E ^b   Leroux, Michel R ^a  

^a SIMON FRASER UNIVERSITY   (Canada)

^b UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

cilia; ciliary gate; MKS5; PIP2; transition zone

Indexed keywords

CAENORHABDITIS ELEGANS PROTEIN; CELL PROTEIN; CILIARY SIGNALLING PROTEIN; G PROTEIN COUPLED RECEPTOR; INVERSIN; MEMBRANE PROTEIN; MKS5 PROTEIN; PHOSPHATIDYLINOSITIDE; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; UNCLASSIFIED DRUG; MKS5 PROTEIN, C ELEGANS;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; AXONEME; CAENORHABDITIS ELEGANS; CELL COMPARTMENTALIZATION; CELL INTERACTION; CELL MEMBRANE; CILIARY BODY; CILIARY ZONE OF EXCLUSION; CONTROLLED STUDY; CRYSTAL STRUCTURE; EUKARYOTIC FLAGELLUM; KINETOSOME; NONHUMAN; PHASE TRANSITION; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TRANSITION ZONE; ULTRASTRUCTURE; ANIMAL; BIOLOGICAL MODEL; FLUORESCENCE; GENE INACTIVATION; GENETICS; GENOTYPE; MEMBRANE STRUCTURE; METABOLISM; MISSENSE MUTATION; PHYSIOLOGY; POLYMERASE CHAIN REACTION; TRANSGENIC ANIMAL; TRANSMISSION ELECTRON MICROSCOPY;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; CELL MEMBRANE STRUCTURES; CILIA; FLUORESCENCE; GENE KNOCKOUT TECHNIQUES; GENOTYPE; MICROSCOPY, ELECTRON, TRANSMISSION; MODELS, BIOLOGICAL; MUTATION, MISSENSE; POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 84944411248     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201488044     Document Type: Article

References (85)

1. Arts HH, Doherty D, van Beersum SE, Parisi MA, Letteboer SJ, Gorden NT, Peters TA, Marker T, Voesenek K, Kartono A, Ozyurek H, Farin FM, Kroes HY, Wolfrum U, Brunner HG, Cremers FP, Glass IA, Knoers NV, Roepman R, (2007) Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. Nat Genet 39: 882-888
2. Awata J, Takada S, Standley C, Lechtreck KF, Bellvé KD, Pazour GJ, Fogarty KE, Witman GB, (2014) NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone. J Cell Sci 127: 4714-4727
3. Bae YK, Kim E, L'Hernault SW, Barr MM, (2009) The CIL-1 PI 5-phosphatase localizes TRP Polycystins to cilia and activates sperm in C. Elegans. Curr Biol 19: 1599-1607
4. Baker K, Beales PL, (2009) Making sense of cilia in disease: the human ciliopathies. Am J Med Genet C Semin Med Genet 151C: 281-295
5. Bednarek EM, Schaheen L, Gaubatz J, Jorgensen EM, Fares H, (2007) The plasma membrane calcium ATPase MCA-3 is required for clathrin-mediated endocytosis in scavenger cells of Caenorhabditis elegans. Traffic 8: 543-553
6. Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA, (2011) Centrosomes and cilia in human disease. Trends Genet 27: 307-315
7. Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, et al, (2009) Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet 41: 1032-1036
8. Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, Johnsen RC, Audeh M, Plasterk RH, Baillie DL, Katsanis N, Quarmby LM, Wicks SR, Leroux MR, (2004) Loss of C. Elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev 18: 1630-1642
9. Blacque OE, Perens EA, Boroevich KA, Inglis PN, Li C, Warner A, Khattra J, Holt RA, Ou G, Mah AK, McKay SJ, Huang P, Swoboda P, Jones SJ, Marra MA, Baillie DL, Moerman DG, Shaham S, Leroux MR, (2005) Functional genomics of the cilium, a sensory organelle. Curr Biol 15: 935-941
10. Boldt K, Mans DA, Won J, van Reeuwijk J, Vogt A, Kinkl N, Letteboer SJ, Hicks WL, Hurd RE, Naggert JK, Texier Y, den Hollander AI, Koenekoop RK, Bennett J, Cremers FP, Gloeckner CJ, Nishina PM, Roepman R, Ueffing M, (2011) Disruption of intraflagellar protein transport in photoreceptor cilia causes Leber congenital amaurosis in humans and mice. J Clin Invest 121: 2169-2180
11. Brenner S, (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71-94
12. Cantagrel V, Silhavy JL, Bielas SL, Swistun D, Marsh SE, Bertrand JY, Audollent S, Attié-Bitach T, Holden KR, Dobyns WB, Traver D, Al-Gazali L, Ali BR, Lindner TH, Caspary T, Otto EA, Hildebrandt F, Glass IA, Logan CV, Johnson CA, et al, (2008) Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. Am J Hum Genet 83: 170-179
13. Cevik S, Sanders AAWM, Van Wijk E, Boldt K, Clarke L, van Reeuwijk J, Hori Y, Horn N, Hetterschijt L, Wdowicz A, Mullins A, Kida K, Kaplan OI, van Beersum SEC, Wu KM, Letteboer SJF, Mans DA, Katada T, Kontani K, Ueffing M, et al, (2013) Active transport and diffusion barriers restrict joubert syndrome-associated ARL13B/ARL-13 to an inv-like ciliary membrane subdomain. PLoS Genet 9: e1003977
14. Chen N, Mah A, Blacque OE, Chu J, Phgora K, Bakhoum MW, Newbury CR, Khattra J, Chan S, Go A, Efimenko E, Johnsen R, Phirke P, Swoboda P, Marra M, Moerman DG, Leroux MR, Baillie DL, Stein LD, (2006) Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics. Genome Biol 7: R126
15. Chih B, Liu P, Chinn Y, Chalouni C, Komuves LG, Hass PE, Sandoval W, Peterson AS, (2012) A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nat Cell Biol 14: 61-72
16. Christensen ST, Clement CA, Satir P, Pedersen LB, (2012) Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling. J Pathol 226: 172-184
17. Coburn CM, Bargmann CI, (1996) A putative cyclic nucleotide-gated channel is required for sensory development and function in C. Elegans. Neuron 17: 695-706
18. Coene KL, Mans DA, Boldt K, Gloeckner CJ, van Reeuwijk J, Bolat E, Roosing S, Letteboer SJ, Peters TA, Cremers FP, Ueffing M, Roepman R, (2011) The ciliopathy-associated protein homologs RPGRIP1 and RPGRIP1L are linked to cilium integrity through interaction with Nek4 serine/threonine kinase. Hum Mol Genet 20: 3592-3605
19. Coon BG, Hernandez V, Madhivanan K, Mukherjee D, Hanna CB, Barinaga-Rementeria Ramirez I, Lowe M, Beales PL, Aguilar RC, (2012) The lowe syndrome protein OCRL1 is involved in primary cilia assembly. Hum Mol Genet 21: 1835-1847
20. Craige B, Tsao CC, Diener DR, Hou Y, Lechtreck KF, Rosenbaum JL, Witman GB, (2010) CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content. J Cell Biol 190: 927-940
21. Czech MP, (2000) PIP2 and PIP3: complex roles at the cell surface. Cell 100: 603-606
22. Deane JA, Cole DG, Seeley ES, Diener DR, Rosenbaum JL, (2001) Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles. Curr Biol 11: 1586-1590
23. Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, Golzio C, Lacoste T, Besse L, Ozilou C, Moutkine I, Hellman NE, Anselme I, Silbermann F, Vesque C, Gerhardt C, Rattenberry E, Wolf MT, Gubler MC, Martinovic J, et al, (2007) The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet 39: 875-881
24. Demmel L, Schmidt K, Lucast L, Havlicek K, Zankel A, Koestler T, Reithofer V, de Camilli P, Warren G, (2014) The endocytic activity of the flagellar pocket in Trypanosoma brucei is regulated by an adjacent phosphatidylinositol phosphate kinase. J Cell Sci 127: 2351-2364
25. Drummond IA, (2012) Cilia functions in development. Curr Opin Cell Biol 24: 24-30
26. Emmer BT, Maric D, Engman DM, (2010) Molecular mechanisms of protein and lipid targeting to ciliary membranes. J Cell Sci 123 (Pt 4): 529-536
27. 2+ and PIP2 recognition by its C2 domain. Mol Biol Cell 17: 56-66
28. Fisch C, Dupuis-Williams P, (2011) Ultrastructure of cilia and flagella-back to the future!. Biol Cell 103: 249-270
29. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, Noriega TR, Seol AD, Robinson JF, Bennett CL, Josifova DJ, Garcia-Verdugo JM, Katsanis N, Hildebrandt F, Reiter JF, (2011) A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet 43: 776-784
30. Garcia-Gonzalo FR, Reiter JF, (2012) Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J Cell Biol 197: 697-709
31. Gerdes JM, Davis EE, Katsanis N, (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137: 32-45
32. Gilula NB, Satir P, (1972) The ciliary necklace. A ciliary membrane specialization. J Cell Biol 53: 494-509
33. Goetz SC, Anderson KV, (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11: 331-344
34. Hedgecock EM, Culotti JG, Thomson JN, Perkins LA, (1985) Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Dev Biol 111: 158-170
35. Hildebrandt F, Benzing T, Katsanis N, (2011) Ciliopathies. N Engl J Med 364: 1533-1543
36. Hu Q, Milenkovic L, Jin H, Scott MP, Nachury MV, Spiliotis ET, Nelson WJ, (2010) A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 329: 436-439
37. 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, Muller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, et al, (2011) 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 89: 713-730
38. Humbert MC, Weihbrecht K, Searby CC, Li Y, Pope RM, Sheffield VC, Seo S, (2012) ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proc Natl Acad Sci USA 109: 19691-19696
39. Inglis PN, Blacque OE, Leroux MR, (2009) Functional genomics of intraflagellar transport-associated proteins in C. Elegans. Methods Cell Biol 93: 267-304
40. Jacoby M, Cox JJ, Gayral S, Hampshire DJ, Ayub M, Blockmans M, Pernot E, Kisseleva MV, Compère P, Schiffmann SN, Gergely F, Riley JH, Pérez-Morga D, Woods CG, Schurmans S, (2009) INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat Genet 41: 1027-1031
41. Jauregui AR, Nguyen KC, Hall DH, Barr MM, (2008) The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure. J Cell Biol 180: 973-988
42. Johnson JL, Leroux MR, (2010) cAMP and cGMP signaling: sensory systems with prokaryotic roots adopted by eukaryotic cilia. Trends Cell Biol 20: 435-444
43. Keady BT, Le YZ, Pazour GJ, (2011) IFT20 is required for opsin trafficking and photoreceptor outer segment development. Mol Biol Cell 22: 921-930
44. Khanna H, Davis EE, Murga-Zamalloa CA, Estrada-Cuzcano A, Lopez I, den Hollander AI, Zonneveld MN, Othman MI, Waseem N, Chakarova CF, Maubaret C, Diaz-Font A, Macdonald I, Muzny DM, Wheeler DA, Morgan M, Lewis LR, Logan CV, Tan PL, Beer MA, et al, (2009) A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies. Nat Genet 41: 739-745
45. Kim K, Sato K, Shibuya M, Zeiger DM, Butcher RA, Ragains JR, Clardy J, Touhara K, Sengupta P, (2009) Two chemoreceptors mediate developmental effects of dauer pheromone in C. Elegans. Science 326: 994-998
46. Komatsu H, Mori I, Rhee JS, Akaike N, Ohshima Y, (1996) Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. Elegans. Neuron 17: 707-718
47. Lee JE, Gleeson JG, (2011) Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr Opin Neurol 24: 98-105
48. Lee JH, Silhavy JL, Lee JE, Al-Gazali L, Thomas S, Davis EE, Bielas SL, Hill KJ, Iannicelli M, Brancati F, Gabriel SB, Russ C, Logan CV, Sharif SM, Bennett CP, Abe M, Hildebrandt F, Diplas BH, Attie-Bitach T, Katsanis N, et al, (2012) Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science 335: 966-969
49. Liu L, Zhang M, Xia Z, Xu P, Chen L, Xu T, (2011) Caenorhabditis elegans ciliary protein NPHP-8, the homologue of human RPGRIP1L, is required for ciliogenesis and chemosensation. Biochem Biophys Res Commun 410: 626-631
50. Luo N, West CC, Murga-Zamalloa CA, Sun L, Anderson RM, Wells CD, Weinreb RN, Travers JB, Khanna H, Sun Y, (2012) OCRL localizes to the primary cilium: a new role for cilia in Lowe syndrome. Hum Mol Genet 21: 3333-3344
51. Luo N, Kumar A, Conwell M, Weinreb RN, Anderson R, Sun Y, (2013) Compensatory role of inositol 5-phosphatase INPP5B to OCRL in primary cilia formation in oculocerebrorenal syndrome of Lowe. PLoS ONE 8: e66727
52. Macosko EZ, Pokala N, Feinberg EH, Chalasani SH, Butcher RA, Clardy J, Bargmann CI, (2009) A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. Elegans. Nature 458: 1171-1175
53. 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, (2010) The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia. J Cell Sci 123: 1785-1795
54. Mukhopadhyay S, Wen X, Chih B, Nelson CD, Lane WS, Scales SJ, Jackson PK, (2010) TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. Genes Dev 24: 2180-2193
55. Nalefski EA, Falke JJ, (1996) The C2 domain calcium-binding motif: structural and functional diversity. Protein Sci 5: 2375-2390
56. Nigg EA, Raff JW, (2009) Centrioles, centrosomes, and cilia in health and disease. Cell 139: 663-678
57. Novarino G, Akizu N, Gleeson JG, (2011) Modeling human disease in humans: the ciliopathies. Cell 147: 70-79
58. Oh EC, Katsanis N, (2012) Cilia in vertebrate development and disease. Development 139: 443-448
59. Patil H, Tserentsoodol N, Saha A, Hao Y, Webb M, Ferreira PA, (2012) Selective loss of RPGRIP1-dependent ciliary targeting of NPHP4, RPGR and SDCCAG8 underlies the degeneration of photoreceptor neurons. Cell Death Dis 3: e355
60. Pazour GJ, Bloodgood RA, (2008) Targeting proteins to the ciliary membrane. Curr Top Dev Biol 85: 115-149
61. Pedersen LB, Rosenbaum JL, (2008) Intraflagellar transport (IFT) role in ciliary assembly, resorption and signalling. Curr Top Dev Biol 85: 23-61
62. Perkins LA, Hedgecock EM, Thomson JN, Culotti JG, (1986) Mutant sensory cilia in the nematode Caenorhabditis elegans. Dev Biol 117: 456-487
63. Quarmby LM, Yueh YG, Cheshire JL, Keller LR, Snell WJ, Crain RC, (1992) Inositol phospholipid metabolism may trigger flagellar excision in Chlamydomonas reinhardtii. J Cell Biol 116: 737-744
64. Reiter JF, Blacque OE, Leroux MR, (2012) The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization. EMBO Rep 13: 608-618
65. Roberson EC, Dowdle WE, Ozanturk A, Garcia-Gonzalo FR, Li C, Halbritter J, Elkhartoufi N, Porath JD, Cope H, Ashley-Koch A, Gregory S, Thomas S, Sayer JA, Saunier S, Otto EA, Katsanis N, Davis EE, Attié-Bitach T, Hildebrandt F, Leroux MR, et al, (2015) TMEM231, mutated in orofaciodigital and Meckel syndromes, organizes the ciliary transition zone. J Cell Biol 209: 129-142
66. Roepman R, Letteboer SJ, Arts HH, van Beersum SE, Lu X, Krieger E, Ferreira PA, Cremers FP, (2005) Interaction of nephrocystin-4 and RPGRIP1 is disrupted by nephronophthisis or Leber congenital amaurosis-associated mutations. Proc Natl Acad Sci USA 102: 18520-18525
67. 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, O'Toole JF, Held S, Reutter HM, et al, (2011) Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 145: 513-528
68. Satir P, Christensen ST, (2007) Overview of structure and function of mammalian cilia. Annu Rev Physiol 69: 377-400
69. Sengupta P, Chou JH, Bargmann CI, (1996) odr-10 encodes a seven transmembrane domain olfactory receptor required for responses to the odorant diacetyl. Cell 84: 899-909
70. Starich TA, Herman RK, Kari CK, Yeh WH, Schackwitz WS, Schuyler MW, Collet J, Thomas JH, Riddle DL, (1995) Mutations affecting the chemosensory neurons of Caenorhabditis elegans. Genetics 139: 171-188
71. Stommel EW, Stephens RE, (1985) Calcium-dependent phosphatidylinositol phosphorylation in lamellibranch gill lateral cilia. J Comp Physiol 157: 441-449
72. Suchard SJ, Rhoads DE, Kaneshiro ES, (1989) The inositol lipids of Paramecium tetraurelia and preliminary characterizations of phosphoinositide kinase activity in the ciliary membrane. J Protozool 36: 185-190
73. Thomas S, Legendre M, Saunier S, Bessières B, Alby C, Bonnière M, Toutain A, Loeuillet L, Szymanska K, Jossic F, Gaillard D, Yacoubi MT, Mougou-Zerelli S, David A, Barthez MA, Ville Y, Bole-Feysot C, Nitschke P, Lyonnet S, Munnich A, et al, (2012) TCTN3 mutations cause Mohr-Majewski syndrome. Am J Hum Genet 91: 372-378
74. Trimble WS, Grinstein S, (2015) Barriers to the free diffusion of proteins and lipids in the plasma membrane. J Cell Biol 208: 259-271
75. 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, et al, (2010) Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet 42: 619-625
76. Veland IR, Awan A, Pedersen LB, Yoder BK, Christensen ST, (2009) Primary cilia and signaling pathways in mammalian development, health and disease. Nephron Physiol 111: 39-53
77. Wallingford JB, Mitchell B, (2011) Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. Genes Dev 25: 201-213
78. Warburton-Pitt SR, Jauregui AR, Li C, Wang J, Leroux MR, Barr MM, (2012) Ciliogenesis in Caenorhabditis elegans requires genetic interactions between ciliary middle segment localized NPHP-2 (inversin) and transition zone-associated proteins. J Cell Sci 125: 2592-2603
79. Williams CL, Winkelbauer ME, Schafer JC, Michaud EJ, Yoder BK, (2008) Functional redundancy of the B9 proteins and nephrocystins in C. Elegans ciliogenesis. Mol Biol Cell 19: 2154-2168
80. Williams CL, Masyukova SV, Yoder BK, (2010) Normal ciliogenesis requires synergy between the cystic kidney disease genes MKS-3 and NPHP-4. J Am Soc Nephrol 21: 782-793
81. Williams CL, Li C, Kida K, Inglis PN, Mohan S, Semenec L, Bialas NJ, Stupay RM, Chen N, Blacque OE, Yoder BK, Leroux MR, (2011) MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function during ciliogenesis. J Cell Biol 192: 1023-1041
82. Winkelbauer ME, Schafer JC, Haycraft CJ, Swoboda P, Yoder BK, (2005) The C. Elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception. J Cell Sci 118: 5575-5587
83. Wong SY, Reiter JF, (2008) The primary cilium at the crossroads of Mammalian hedgehog signaling. Curr Top Dev Biol 85: 225-260
84. Zhang D, Aravind L, (2012) Novel transglutaminase-like peptidase and C2 domains elucidate the structure, biogenesis and evolution of the ciliary compartment. Cell Cycle 11: 3861-3875
85. Zhao C, Malicki J, (2011) Nephrocystins and MKS proteins interact with IFT particle and facilitate transport of selected ciliary cargos. EMBO J 30: 2532-2544