The Ciliopathy Protein CC2D2A Associates with NINL and Functions in RAB8-MICAL3-Regulated Vesicle Trafficking

PLoS Genetics

Volumn 11, Issue 10, 2015, Pages

  Bachmann Gagescu, Ruxandra ^a   Dona, Margo ^b,c   Hetterschijt, Lisette ^b,c   Tonnaer, Edith ^b   Peters, Theo ^b   de Vrieze, Erik ^b,c   Mans, Dorus A ^b,c   van Beersum, Sylvia E C ^b,c   Phelps, Ian G ^d   Arts, Heleen H ^b,c,e   Keunen, Jan E ^b   Ueffing, Marius ^f   Roepman, Ronald ^b,c   Boldt, Karsten ^f   Doherty, Dan ^d   Moens, Cecilia B ^g   Neuhauss, Stephan C F ^a   Kremer, Hannie ^b,c   van Wijk, Erwin ^b,c  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF WESTERN ONTARIO   (Canada)

^f UNIVERSITY OF TÜBINGEN   (Germany)

^g USA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEAR PROTEIN; OPSIN; PROTEIN CC2D2A; PROTEIN NINL; PROTEIN RAB8; UNCLASSIFIED DRUG; CC2D2A PROTEIN, HUMAN; MICAL3 PROTEIN, HUMAN; MICROTUBULE ASSOCIATED PROTEIN; MIXED FUNCTION OXIDASE; NIP PROTEIN, HUMAN; PROTEIN; RAB PROTEIN; RAB8A PROTEIN, HUMAN;

ARTICLE; CC2D2A GENE; CELL DEATH; CILIARY BODY; EXON; GENE; GENE FREQUENCY; GENE MUTATION; HETEROZYGOSITY; HOMOZYGOSITY; JOUBERT SYNDROME; NONHUMAN; PHENOTYPE; PHOTORECEPTOR CELL; PHOTORECEPTOR OUTER SEGMENT; PROTEIN CONTENT; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; RETINA; TRANSPORT VESICLE; ABNORMALITIES; ANIMAL; CEREBELLUM; CILIARY DYSKINESIA; ENCEPHALOCELE; EUKARYOTIC FLAGELLUM; EYE MALFORMATION; GENE SILENCING; GENETICS; HUMAN; KIDNEY POLYCYSTIC DISEASE; METABOLISM; MULTIPLE MALFORMATION SYNDROME; MUTATION; PATHOLOGY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; ZEBRA FISH;

ABNORMALITIES, MULTIPLE; ANIMALS; CEREBELLUM; CILIA; CILIARY MOTILITY DISORDERS; ENCEPHALOCELE; EYE ABNORMALITIES; GENE KNOCKDOWN TECHNIQUES; HUMANS; KIDNEY DISEASES, CYSTIC; MICROTUBULE-ASSOCIATED PROTEINS; MIXED FUNCTION OXYGENASES; MUTATION; NUCLEAR PROTEINS; POLYCYSTIC KIDNEY DISEASES; PROTEIN TRANSPORT; PROTEINS; RAB GTP-BINDING PROTEINS; RETINA; SIGNAL TRANSDUCTION; ZEBRAFISH;

EID: 84946600791     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1005575     Document Type: Article

References (58)

1. Goetz SC, Anderson KV, The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010; 11 (5): 331–344. doi: 10.1038/nrg2774 20395968
2. Tyler KM, Fridberg A, Toriello KM, Olson CL, Cieslak JA, et al. Flagellar membrane localization via association with lipid rafts. J Cell Sci. 2009; 122 (6): 859–866.
3. Hu Q, Milenkovic L, Jin H, Scott MP, Nachury MV, et al. A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution. Science. 2010; 329 (5990): 436–439. doi: 10.1126/science.1191054 20558667
4. 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 (1): 59–87.
5. Williams CL, Li C, Kida K, Inglis PN, Mohan S, 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 (6): 1023–1041. doi: 10.1083/jcb.201012116 21422230
6. 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 reports. 2012; 13 (7): 608–618. doi: 10.1038/embor.2012.73 22653444
7. Garcia-Gonzalo FR, Corbit KC, Sirerol-Piquer MS, Ramaswami G, Otto EA, et al. A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nat Genet. 2011; 43 (8): 776–784. doi: 10.1038/ng.891 21725307
8. Hildebrandt F, Benzing T, Katsanis N, Ciliopathies. N Engl J Med. 2011; 364 (16): 1533–1543. doi: 10.1056/NEJMra1010172 21506742
9. Badano JL, Mitsuma N, Beales PL, Katsanis N, The Ciliopathies: An Emerging Class of Human Genetic Disorders. Annu Rev Genom Human Genet. 2006; 7 (1): 125–148.
10. Insinna C, Besharse JC, Intraflagellar transport and the sensory outer segment of vertebrate photoreceptors. Dev Dyn. 2008; 237 (8): 1982–1992. doi: 10.1002/dvdy.21554 18489002
11. Parisi MA, Glass I, Joubert syndrome and related disorders. Genereviews. 2003. http://www.ncbi.nlm.nih.gov/boooks/NBK1325/
12. Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, et al. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity. J Med Genet. 2015; 52 (8): 514–22. doi: 10.1136/jmedgenet-2015-103087 26092869
13. Maria BL, Hoang KBN, Tusa RJ, Mancuso AA, Hamed LM, et al. "Joubert Syndrome" Revisited: Key Ocular Motor Signs With Magnetic Resonance Imaging Correlation. J Child Neurol. 1997; 12 (7): 423–430. 9373798
14. Romani M, Micalizzi A, Valente EM, Joubert syndrome: congenital cerebellar ataxia with the molar tooth. Lancet Neurol. 2013; 12 (9): 894–905. doi: 10.1016/S1474-4422(13)70136-4 23870701
15. Doherty D, Joubert Syndrome: Insights Into Brain Development, Cilium Biology, and Complex Disease. Semin Pediatr Neurol. 2009; 16 (3): 143–154. doi: 10.1016/j.spen.2009.06.002 19778711
16. Romani M, Micalizzi A, Valente EM, Joubert syndrome: congenital cerebellar ataxia with the molar tooth. Lancet Neurol. 2013; 12 (9): 894–905. doi: 10.1016/S1474-4422(13)70136-4 23870701
17. Romani M, Micalizzi A, Kraoua I, Dotti M, Cavallin M, et al. Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome. Orphanet J Rare Dis. 2014;9 (1): 72.
18. Tuz K, Bachmann-Gagescu R, O’Day DR, Hua K, Isabella CR, et al. Mutations in CSPP1 Cause Primary Cilia Abnormalities and Joubert Syndrome with or without Jeune Asphyxiating Thoracic Dystrophy. Am J Hum Genet. 2014; 94 (1): 62–72. doi: 10.1016/j.ajhg.2013.11.019 24360808
19. Bachmann-Gagescu R, Phelps IG, Dempsey JC, Sharma VA, Ishak GE, et al. KIAA0586 is mutated in Joubert Syndrome.Hum Mutat. 2015; 36 (9): 831–5. doi: 10.1002/humu.22821 26096313
20. Thomas S, Wright KJ, Le Corre S, Micalizzi A, Romani M, et al. A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium. Hum Mutat. 2014; 35 (1): 137–146. 24166846
21. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, et al. Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and Pathways. Cell. 2011; 145 (4): 513–528. doi: 10.1016/j.cell.2011.04.019 21565611
22. Bachmann-Gagescu R, Ishak GE, Dempsey JC, Adkins J, O'Day D, et al. Genotype–phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures. J Med Genet. 2012; 49 (2): 126–137. doi: 10.1136/jmedgenet-2011-100552 22241855
23. Mougou-Zerelli S, Thomas S, Szenker E, Audollent S, Elkhartoufi N, et al. CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype–phenotype correlation. Hum Mutat. 2009; 30 (11): 1574–1582. doi: 10.1002/humu.21116 19777577
24. Veleri S, Manjunath SH, Fariss RN, May-Simera H, Brooks M, et al. Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis. Nat Commun. 2014; 20 (5):4207.
25. Bachmann-Gagescu R, Phelps IG, Stearns G, Link BA, Brockerhoff SE, et al. The ciliopathy gene cc2d2a controls zebrafish photoreceptor outer segment development through a role in Rab8-dependent vesicle trafficking. Hum Mol Genet. 2011; 20 (20): 4041–4055. doi: 10.1093/hmg/ddr332 21816947
26. Deretic D, Wang J, Molecular assemblies that control rhodopsin transport to the cilia. Vision Res. 2012; 75 (0): 5–10.
27. Moritz OL, Tam BM, Hurd LL, Peränen J, Deretic D, et al. Mutant rab8 Impairs Docking and Fusion of Rhodopsin-bearing Post-Golgi Membranes and Causes Cell Death of TransgenicXenopus Rods. Mol Biol Cell. 2001; 12 (8): 2341–2351. 11514620
28. Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peränen J, et al. A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis. Cell. 2007; 129 (6): 1201–1213. 17574030
29. Westlake CJ, Baye LM, Nachury MV, Wright KJ, Ervin KE, et al. Primary cilia membrane assembly is initiated by Rab11 and transport protein particle II (TRAPPII) complex-dependent trafficking of Rabin8 to the centrosome. PNAS. 2011; 108 (7): 2759–2764. doi: 10.1073/pnas.1018823108 21273506
30. Cevik S, Sanders AAWM, van Wijk E, Boldt K, Clarke L, 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 (12): e1003977 EP. doi: 10.1371/journal.pgen.1003977 24339792
31. van Wijk E, Kersten FFJ, Kartono A, Mans DA, Brandwijk K, et al. Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein. Hum Mol Genet. 2009; 18 (1): 51–64. doi: 10.1093/hmg/ddn312 18826961
32. Ben J, Elworthy S, Ng ASM, van Eeden F, Ingham PW, Targeted mutation of the talpid3 gene in zebrafish reveals its conserved requirement for ciliogenesis and Hedgehog signalling across the vertebrates. Development. 2011; 138 (22): 4969–4978. doi: 10.1242/dev.070862 22028029
33. O’Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, et al. Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders. Science. 2012; 338 (6114): 1619–1622. doi: 10.1126/science.1227764 23160955
34. Doherty D, Parisi MA, Finn LS, Gunay-Aygun M, Al-Mateen M, et al. Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis). J Med Genet. 2010; 47 (1): 8–21. doi: 10.1136/jmg.2009.067249 19574260
35. Wang J, Deretic D, Molecular complexes that direct rhodopsin transport to primary cilia. Prog Retin Eye Res. 2014; 38 (0): 1–19.
36. Wang J, Morita Y, Mazelova J, Deretic D, The Arf GAP ASAP1 provides a platform to regulate Arf4‐ and Rab11–Rab8‐mediated ciliary receptor targeting. EMBO J. 2012; 31 (20): 4057–4071. doi: 10.1038/emboj.2012.253 22983554
37. Gloeckner CJ, Boldt K, Schumacher A, Roepman R, Ueffing M, A novel tandem affinity purification strategy for the efficient isolation and characterisation of native protein complexes. Proteomics. 2007; 7 (23): 4228–4234. 17979178
38. Rothschild SC, Francescatto L, Drummond IA, Tombes RM, CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia. Development. 2011; 138 (16): 3387–3397. doi: 10.1242/dev.066340 21752935
39. Grigoriev I, Yu KL, Martinez-Sanchez E, Serra-Marques A, Smal I, et al. Rab6, Rab8, and MICAL3 Cooperate in Controlling Docking and Fusion of Exocytotic Carriers. Curr Biol. 2011; 21 (11): 967–974. doi: 10.1016/j.cub.2011.04.030 21596566
40. Wolfrum U1, Liu X, Schmitt A, Udovichenko IP, Williams DS, Myosin VIIa as a common component of cilia and microvilli. Cell Motil Cytoskeleton. 1998; 40 (3): 261–271. 9678669
41. Maerker T, van Wijk E, Overlack N, Kersten FFJ, McGee J, et al. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet. 2008; 17 (1): 71–86. 17906286
42. van Wijk E, van der Zwaag B, Peters T, Zimmermann U, te Brinke H, et al. The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum Mol Genet. 2006; 15 (5): 751–765. 16434480
43. Kremer H, van Wijk E, Märker T, Wolfrum U, Roepman R, Usher syndrome: molecular links of pathogenesis, proteins and pathways. Hum Mol Genet. 2006; 15 (suppl 2): R262.
44. Madhivanan K, Aguilar RC, Ciliopathies: The Trafficking Connection. Traffic. 2014; 15 (10): 1031–1056. doi: 10.1111/tra.12195 25040720
45. Hsiao Y, Tuz K, Ferland R, (2012) Trafficking in and to the primary cilium. Cilia 1 (1): 4. doi: 10.1186/2046-2530-1-4 23351793
46. Kennedy B, Malicki J, What drives cell morphogenesis: A look inside the vertebrate photoreceptor. Dev Dyn. 2009; 238 (9): 2115–2138. doi: 10.1002/dvdy.22010 19582864
47. Casenghi M, Barr FA, Nigg EA, Phosphorylation of Nlp by Plk1 negatively regulates its dynein-dynactin-dependent targeting to the centrosome. J Cell Sci. 2005; 118 (21): 5101–5108.
48. Kim J, Krishnaswami SR, Gleeson JG, CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. Hum Mol Genet. 2008; 17 (23): 3796–3805. doi: 10.1093/hmg/ddn277 18772192
49. Murga-Zamalloa CA, Atkins SJ, Peranen J, Swaroop A, Khanna H, Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration. Hum Mol Genet. 2010; 19 (18): 3591–3598. doi: 10.1093/hmg/ddq275 20631154
50. Westerfield M, The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). University of Oregon Press, Eugene, OR; 2000.
51. Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, et al. Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death. PLoS Genet. 2008; 4 (2): e1000020 EP. doi: 10.1371/journal.pgen.1000020 18454195
52. Gorden NT, Arts HH, Parisi MA, Coene KLM, Letteboer SJF, et al. CC2D2A Is Mutated in Joubert Syndrome and Interacts with the Ciliopathy-Associated Basal Body Protein CEP290. Am J Hum Genet. 2008; 83 (5): 559–571. doi: 10.1016/j.ajhg.2008.10.002 18950740
53. Perner B, Englert C, Bollig F, The Wilms tumor genes wt1a and wt1b control different steps during formation of the zebrafish pronephros. Dev Bio. 2007; 309 (1): 87–96.
54. Letteboer SF, Roepman R, Thompson J, Ueffing M, Schaeffer-Reiss C, (2008) Versatile Screening for Binary Protein-Protein Interactions by Yeast Two-Hybrid Mating. In: Functional Proteomics: Humana Press. pp. 145–159; 2008.
55. Bendall SC, Hughes C, Stewart MH, Doble B, Bhatia M, et al. Prevention of Amino Acid Conversion in SILAC Experiments with Embryonic Stem Cells. Mol Cell Proteomics. 2008; 7 (9): 1587–1597. doi: 10.1074/mcp.M800113-MCP200 18487603
56. den Hollander AI, Koenekoop RK, Mohamed MD, Arts HH, Boldt K, et al. Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. Nat Genet. 2007; 39 (7): 889–895. 17546029
57. Gloeckner CJ, Boldt K, Ueffing M, Strep/FLAG Tandem Affinity Purification (SF-TAP) to Study Protein Interactions. Current Protocols in Protein Science: John Wiley & Sons Inc.; 2001.
58. Krock BL, Perkins BD, The intraflagellar transport protein IFT57 is required for cilia maintenance and regulates IFT-particle–kinesin-II dissociation in vertebrate photoreceptors. J Cell Sci. 2008; 121 (11): 1907–1915.