Abstract
The protein CEP290 has recently emerged as a major player in the biology of the cilium and as a causative protein in a number of human syndromic diseases, most of which are associated with the devastating blinding disease Leber congenital amaurosis. (Coppieters et al., Hum Mutat 31, 2010, 1097–1108) CEP290 is known to be an important component of the primary cilium, localizing to the Y-links of the ciliary transition zone and having a role in the regulation of transport in and out of the ciliary compartment (Craige et al., J Cell Biol 190, 2010, 927–940). While many mutations in CEP290 have been identified in human patients, how these mutations result in the spectrum of human disease attributed to the protein remain unknown. As we begin to learn more about the normal role of CEP290, it is likely that we will begin to shed light on how these mutations result in the various CEP290 disease phenotypes. Here we discuss many of these diverse aspects of CEP290 biology and pathology in an attempt to link what we know about the molecular mechanisms of CEP290 function with what we know about CEP290-asociated disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Coppieters F, Lefever S, Leroy BP, De Baere E (2010) CEP290, a gene with many faces: mutation overview and presentation of CEP290base. Hum Mutat 31:1097–1108
Craige B et al (2010) CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content. J Cell Biol 190:927–940
Gerdes JM, Davis EE, Katsanis N (2009) The vertebrate primary cilium in development, homeostasis, and disease. Cell 137:32–45
Qin H (2012) Regulation of intraflagellar transport and ciliogenesis by small G proteins. Int Rev Cell Mol Biol 293:149–168
Waters AM, Beales PL (2011) Ciliopathies: an expanding disease spectrum. Pediatr Nephrol 26:1039–1056
Chang B et al (2006) 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 15:1847–1857
Moradi P, Davies WL, Mackay DS, Cheetham ME, Moore AT (2011) Focus on molecules: centrosomal protein 290 (CEP290). Exp Eye Res 92:316–317
Tsang WY et al (2008) CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease. Dev Cell 15:187–197
Sayer JA et al (2006) The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet 38:674–681
Zhao Y et al (2003) The retinitis pigmentosa GTPase regulator (RPGR)- interacting protein: subserving RPGR function and participating in disk morphogenesis. Proc Natl Acad Sci USA 100:3965–3970
Murga-Zamalloa CA, Atkins SJ, Peranen J, Swaroop A, Khanna H (2010) Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration. Hum Mol Genet 19:3591–3598
Kim J, Krishnaswami SR, Gleeson JG (2008) CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium. Hum Mol Genet 17:3796–3805
Schäfer T et al (2008) Genetic and physical interaction between the NPHP5 and NPHP6 gene products. Hum Mol Genet 17:3655–3662
Den Hollander AI et al (2006) Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet 79:556–561
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this paper
Cite this paper
Drivas, T., Bennett, J. (2014). CEP290 and the Primary Cilium. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_66
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3209-8_66
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3208-1
Online ISBN: 978-1-4614-3209-8
eBook Packages: MedicineMedicine (R0)