Abstract
The outer segments of photoreceptor cells are specialized sensory cilia, and share many features with other primary and sensory cilia. Like other cilia, photoreceptor sensory cilium (PSC) comprises a membrane domain of outer segment and its cytoskeleton. We have recently identified the protein components of mouse PSCs, and found that the list of PSC proteins, called the PSC proteome, contains many novel cilia proteins. Studies have shown that many of the identified retinal degeneration disease genes encode proteins which are part of the PSC. Furthermore, mutations in genes encoding proteins expressed both in photoreceptors and other cilia result in systemic diseases, such as Usher syndrome, Bardet-Biedl syndrome (BBS), and Senior-Loken syndrome that involve retinal degeneration along with other disorders consequent to cilia dysfunction such as deafness and polycystic kidney disease. Based on these findings, we hypothesize that genes that encode proteins required for formation of PSCs are good candidate retinal degeneration disease genes. This chapter will summarize our studies on identifying novel PSC proteins from the PSC proteome. As an example of these studies, we demonstrated that tetratricopeptide the repeat domain 21B (TTC21B) protein is a novel PSC protein and is required for normal cilia formation in primary and photoreceptor sensory cilia.
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References
Allen RA (1965) Isolated cilia in inner retinal neurons and in retinal pigment epithelium. J Ultrastruct Res 12:730–747
Ansley SJ, Badano JL, Blacque OE et al (2003) Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature 425:628–633
Badano JL, Mitsuma N, Beales PL et al (2006) The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 7:125–148
Berbari NF, Johnson AD, Lewis JS et al (2008) Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell 19:1540–1547
Breunig JJ, Sarkisian MR, Arellano JI et al (2008) Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci USA 105:13127–13132
Cantagrel V, Silhavy JL, Bielas SL et al (2008) Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. Am J Hum Genet 83:170–179
Chang B, Khanna H, Hawes N 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
Christensen ST, Pedersen LB, Schneider L et al (2007) Sensory cilia and integration of signal transduction in human health and disease. Traffic 8:97–109
Daiger SP, Bowne SJ, Sullivan LS (2007) Perspective on genes and mutations causing retinitis pigmentosa. Arch Ophthalmol 125:151–158
Davis EE, Brueckner M, Katsanis N (2006) The emerging complexity of the vertebrate cilium: new functional roles for an ancient organelle. Dev Cell 11:9–19
De Robertis E (1956) Electron microscope observations on the submicroscopic organization of the retinal rods. J Biophys Biochem Cytol 2:319–330
den Hollander AI, Koenekoop RK, Yzer S et al (2006) Mutations in the CEP290 (NPHP6) gene are a frequent cause of leber congenital amaurosis. Am J Hum Genet 79:556–561
den Hollander AI, Koenekoop RK, Mohamed MD et al (2007) Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis. Nat Genet 39: 889–895
Fan Y, Esmail MA, Ansley SJ et al (2004) Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet 36:989–993
Fliegauf M, Horvath J, von SC et al (2006) Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia. J Am Soc Nephrol 17:2424–2433
Gerdes JM, Liu Y, Zaghloul NA et al (2007) Disruption of the basal body compromises proteasomal function and perturbs intracellular Wnt response. Nat Genet 39:1350–1360
Gherman A, Davis EE, Katsanis N (2006) The ciliary proteome database: an integrated community resource for the genetic and functional dissection of cilia. Nat Genet 38:961–962
Giulietti A, Overbergh L, Valckx D et al (2001) An overview of real-time quantitative PCR: applications to quantify cytokine gene expression. Methods 25:386–401
Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809
Hildebrandt F, Zhou W (2007) Nephronophthisis-associated ciliopathies. J Am Soc Nephrol 18:1855–1871
Hong DH, Pawlyk BS, Shang J et al (2000) A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci USA 97:3649–3654
Horst CJ, Johnson LV, Besharse JC (1990) Transmembrane assemblage of the photoreceptor connecting cilium and motile cilium transition zone contain a common immunologic epitope. Cell Motil Cytoskeleton 17:329–344
Jekely G, Arendt D (2006) Evolution of intraflagellar transport from coated vesicles and autogenous origin of the eukaryotic cilium. Bioessays 28:191–198
Kaplan MW, Iwata RT, Sears RC (1987) Lengths of immunolabeled ciliary microtubules in frog photoreceptor outer segments. Exp Eye Res 44:623–632
Liu Q, Zhou J, Daiger SP et al (2002) Identification and Subcellular Localization of the RP1 Protein in Human and Mouse Photoreceptors. Invest Ophthalmol Vis Sci 43:22–32
Liu Q, Zuo J, Pierce EA (2004) The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein. J Neurosci 24:6427–6436
Liu Q, Tan G, Levenkova N et al (2007) The proteome of the mouse photoreceptor sensory cilium complex. Mol Cell Proteomics 6:1299–1317
Liu X, Vansant G, Udovichenko IP et al (1997) Myosin VIIa, the product of the Usher 1B syndrome gene, is concentrated in the connecting cilia of photoreceptor cells. Cell Motil Cytoskeleton 37:240–252
Maerker T, van WE, Overlack N et al (2008) A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum Mol Genet 17:71–86
Maguire AM, Simonelli F, Pierce EA et al (2008) Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med 358:2240–2248
Matsuda T, Cepko CL (2004) Electroporation and RNA interference in the rodent retina in vivo and in vitro. Proc Natl Acad Sci USA 101:16–22
Matsusaka T (1974) Membrane Particles of the Connecting Cilium. J Ultrastruct Res 48:305–312
Otto EA, Loeys B, Khanna H et al (2005) Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat Genet 37:282–288
Pan J, Wang Q, Snell WJ (2005) Cilium-generated signaling and cilia-related disorders. Lab Invest 85:452–463
Reiners J, Marker T, Jurgens K et al (2005a) Photoreceptor expression of the Usher syndrome type 1 protein protocadherin 15 (USH1F) and its interaction with the scaffold protein harmonin (USH1C). Mol Vis 11:347–355
Reiners J, van Wijk E, Marker T et al (2005b) Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum Mol Genet 14:3933–3943
RetNet (2008) RetNet Web site address.
Roepman R, Letteboer SJ, Arts HH et al (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
Sayer JA, Otto EA, O’Toole JF et al (2006) The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet 38:674–681
Simons M, Mlodzik M (2008) Planar cell polarity signaling: from fly development to human disease. Annu Rev Genet 42:517–540
Singla V, Reiter JF (2006) The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313:629–633
Slough J, Cooney L, Brueckner M (2008) Monocilia in the embryonic mouse heart suggest a direct role for cilia in cardiac morphogenesis. Dev Dyn 237:2304–2314
Tran PV, Haycraft CJ, Besschetnova TY et al (2008) THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia. Nat Genet 40:403–410
Tucker RW, Pardee AB, Fujiwara K (1979) Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell 17:527–535
Valente EM, Silhavy JL, Brancati F et al (2006) Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet 38:623–625
Yang J, Gao J, Adamian M et al (2005) The ciliary rootlet maintains long-term stability of sensory cilia. Mol Cell Biol 25:4129–4137
Zhao Y, Hong DH, Pawlyk B 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
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Liu, Q., Zhang, Q., Pierce, E.A. (2010). Photoreceptor Sensory Cilia and Inherited Retinal Degeneration. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_26
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DOI: https://doi.org/10.1007/978-1-4419-1399-9_26
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