CP110 Suppresses Primary Cilia Formation Through Its Interaction with CEP290, a Protein Deficient in Human Ciliary Disease

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2008 Aug 13

PMID 18694559

Citations 163

Authors

William Y Tsang

Carine Bossard

Hemant Khanna

Johan Peranen

Anand Swaroop

Vivek Malhotra

Brian David Dynlacht

Affiliations

Soon will be listed here.

Abstract

Primary cilia are nonmotile organelles implicated in signaling and sensory functions. Understanding how primary cilia assemble could shed light on the many human diseases caused by mutations in ciliary proteins. The centrosomal protein CP110 is known to suppress ciliogenesis through an unknown mechanism. Here, we report that CP110 interacts with CEP290--a protein whose deficiency is implicated in human ciliary disease--in a discrete complex separable from other CP110 complexes involved in regulating the centrosome cycle. Ablation of CEP290 prevents ciliogenesis without affecting centrosome function or cell-cycle progression. Interaction with CEP290 is absolutely required for the ability of CP110 to suppress primary cilia formation. Furthermore, CEP290 and CP110 interact with Rab8a, a small GTPase required for cilia assembly. Depletion of CEP290 interferes with localization of Rab8a to centrosomes and cilia. Our results suggest that CEP290 cooperates with Rab8a to promote ciliogenesis and that this function is antagonized by CP110.

Citing Articles

Ciliopathy-associated protein, CEP290, is required for ciliary necklace and outer segment membrane formation in retinal photoreceptors.

Moye A, Robichaux M, Agosto M, Rivolta C, Moulin A, Wensel T bioRxiv. 2025; .

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Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends.

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Biallelic Variants in LRRC45 Impair Ciliogenesis and Cause a Severe Neurological Disorder.

Radhakrishnan P, Quadri N, Erger F, Fuhrmann N, Geist O, Netzer C Clin Genet. 2024; 107(3):311-322.

PMID: 39638757 PMC: 11790379. DOI: 10.1111/cge.14663.

A polarized multicomponent foundation upholds ciliary central microtubules.

Chen Q, Zhao H, Pan X, Fang C, Qiu B, Guo J J Mol Cell Biol. 2024; 16(8).

PMID: 39165107 PMC: 11781205. DOI: 10.1093/jmcb/mjae031.

Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Lo C, Liu Z, Chen S, Lin F, Berneshawi A, Yu C J Clin Invest. 2024; 134(13).

PMID: 38949024 PMC: 11213510. DOI: 10.1172/JCI175560.

References

Chen D, Shou C . Molecular cloning of a tumor-associated antigen recognized by monoclonal antibody 3H11. Biochem Biophys Res Commun. 2001; 280(1):99-103. DOI: 10.1006/bbrc.2000.4087. View

Tsang W, Wang L, Chen Z, Sanchez I, Dynlacht B . SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression. J Cell Biol. 2007; 178(4):621-33. PMC: 2064469. DOI: 10.1083/jcb.200701166. View

Peranen J, Auvinen P, Virta H, Wepf R, Simons K . Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts. J Cell Biol. 1996; 135(1):153-67. PMC: 2121014. DOI: 10.1083/jcb.135.1.153. View

Scholey J, Anderson K . Intraflagellar transport and cilium-based signaling. Cell. 2006; 125(3):439-42. DOI: 10.1016/j.cell.2006.04.013. View

Helou J, Otto E, Attanasio M, Allen S, Parisi M, Glass I . Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndrome. J Med Genet. 2007; 44(10):657-63. PMC: 2597962. DOI: 10.1136/jmg.2007.052027. View

Follit J, Tuft R, Fogarty K, Pazour G . The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell. 2006; 17(9):3781-92. PMC: 1593158. DOI: 10.1091/mbc.e06-02-0133. View

Valente E, Silhavy J, Brancati F, Barrano G, Krishnaswami S, Castori M . Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet. 2006; 38(6):623-5. DOI: 10.1038/ng1805. View

Bettencourt-Dias M, Glover D . Centrosome biogenesis and function: centrosomics brings new understanding. Nat Rev Mol Cell Biol. 2007; 8(6):451-63. DOI: 10.1038/nrm2180. View

Spektor A, Tsang W, Khoo D, Dynlacht B . Cep97 and CP110 suppress a cilia assembly program. Cell. 2007; 130(4):678-90. DOI: 10.1016/j.cell.2007.06.027. View

10.

Chang B, Khanna H, Hawes N, Jimeno D, He S, Lillo C . In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum Mol Genet. 2006; 15(11):1847-57. PMC: 1592550. DOI: 10.1093/hmg/ddl107. View

11.

Baala L, Audollent S, Martinovic J, Ozilou C, Babron M, Sivanandamoorthy S . Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. Am J Hum Genet. 2007; 81(1):170-9. PMC: 1950929. DOI: 10.1086/519494. View

12.

Singla V, Reiter J . The primary cilium as the cell's antenna: signaling at a sensory organelle. Science. 2006; 313(5787):629-33. DOI: 10.1126/science.1124534. View

13.

Paoletti A, Moudjou M, Paintrand M, Salisbury J, Bornens M . Most of centrin in animal cells is not centrosome-associated and centrosomal centrin is confined to the distal lumen of centrioles. J Cell Sci. 1996; 109 ( Pt 13):3089-102. DOI: 10.1242/jcs.109.13.3089. View

14.

Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof Y, Nigg E . Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007; 13(2):190-202. DOI: 10.1016/j.devcel.2007.07.002. View

15.

Nachury M, Loktev A, Zhang Q, Westlake C, Peranen J, Merdes A . A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell. 2007; 129(6):1201-13. DOI: 10.1016/j.cell.2007.03.053. View

16.

den Hollander A, Koenekoop R, Yzer S, Lopez I, Arends M, Voesenek K . Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet. 2006; 79(3):556-61. PMC: 1559533. DOI: 10.1086/507318. View

17.

Badano J, Teslovich T, Katsanis N . The centrosome in human genetic disease. Nat Rev Genet. 2005; 6(3):194-205. DOI: 10.1038/nrg1557. View

18.

Jurczyk A, Gromley A, Redick S, San Agustin J, Witman G, Pazour G . Pericentrin forms a complex with intraflagellar transport proteins and polycystin-2 and is required for primary cilia assembly. J Cell Biol. 2004; 166(5):637-43. PMC: 2172416. DOI: 10.1083/jcb.200405023. View

19.

Scholey J . Intraflagellar transport. Annu Rev Cell Dev Biol. 2003; 19:423-43. DOI: 10.1146/annurev.cellbio.19.111401.091318. View

20.

Nigg E . Centrosome aberrations: cause or consequence of cancer progression?. Nat Rev Cancer. 2002; 2(11):815-25. DOI: 10.1038/nrc924. View