The photoreceptor outer segment is an elaborate primary cilium. The delivery of opsin into and along the cilium is critical for photoreceptor cell function and viability. The overall goal of this study is to understand the cellular mechanisms involved in these delivery processes. A combination of cell biological methods, including imaging of protein movements in the cilium of live mouse photoreceptor cells, will be used. Studies will address questions about opsin entry into and transport along the cilium, and the membrane diffusion barrier of the photoreceptor cilium. The proposed research incorporates technical innovation, including the measurements of real-time movements of opsin along the cilium, using a ciliated epithelial cell line and mouse rod photoreceptor cells. It will test novel concepts of opsin trafficking and the organization of the photoreceptor cilium.

Public Health Relevance

The proposed research will provide a fundamental mechanistic understanding of cellular processes in the photoreceptor cilium. It will provide insight into the pathogenesis of a wide range of diseases, known as ciliopathies, which include retinal degeneration. There will also be tangible benefits to preclinical studies for retinal degeneration therapies, in that mutant phenotypes, which can be used to assess therapeutic efficacy, are likely to be identified by the research.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (BVS)
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Neuhold, Lisa
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Crouse, Jacquelin A; Lopes, Vanda S; Sanagustin, Jovenal T et al. (2014) Distinct functions for IFT140 and IFT20 in opsin transport. Cytoskeleton (Hoboken) 71:302-10
Zariwala, Maimoona A; Gee, Heon Yung; Kurkowiak, Malgorzata et al. (2013) ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. Am J Hum Genet 93:336-45
Trivedi, Deepti; Williams, David S (2010) Ciliary transport of opsin. Adv Exp Med Biol 664:185-91
Louie, Carrie M; Caridi, Gianluca; Lopes, Vanda S et al. (2010) AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat Genet 42:175-80
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Jimeno, David; Feiner, Leonard; Lillo, Concepcion et al. (2006) Analysis of kinesin-2 function in photoreceptor cells using synchronous Cre-loxP knockout of Kif3a with RHO-Cre. Invest Ophthalmol Vis Sci 47:5039-46
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