Abstract

Kinesins are microtubule motor proteins that generate intracellular movement essential for many fundamental cellular processes. The long-term goal of this project is to understand the function of kinesin-2 in the photoreceptor cilium. The current application is based on three new developments: (1) A newly established model of opsin transport in cilia that can be studied by live-cell imaging;(2) Findings that link known retinal disease genes to kinesin-2 and ciliary transport;and (3) Refinement of the genetic model so that loss of kinesin-2 can be studied prior to photoreceptor cell death. We propose to capitalize upon these new findings and developments by: (1) Testing two competing hypotheses for how kinesin-2 generates opsin transport along the cilium, and testing the roles of different proteins in the transport of opsin along the photoreceptor cilium. (2) Determining the contribution of kinesin-2 in different (non-opsin) transport processes related to the photoreceptor cilium. The results of these studies will lead to a better understanding of critical cellular processes in the photoreceptor cilium, and thus provide important new insight into a major group of inherited retinal degenerations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013408-06
Application #
7935221
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Mariani, Andrew P
Project Start
2009-09-30
Project End
2012-09-29
Budget Start
2010-09-30
Budget End
2012-09-29
Support Year
6
Fiscal Year
2010
Total Cost
$385,000
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Hazim, Roni A; Volland, Stefanie; Yen, Alice et al. (2018) Rapid differentiation of the human RPE cell line, ARPE-19, induced by nicotinamide. Exp Eye Res 179:18-24
Volland, Stefanie; Williams, David S (2018) Preservation of Photoreceptor Nanostructure for Electron Tomography Using Transcardiac Perfusion Followed by High-Pressure Freezing and Freeze-Substitution. Adv Exp Med Biol 1074:603-607
Esteve-Rudd, Julian; Hazim, Roni A; Diemer, Tanja et al. (2018) Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration. Proc Natl Acad Sci U S A 115:5468-5473
Hazim, Roni A; Karumbayaram, Saravanan; Jiang, Mei et al. (2017) Differentiation of RPE cells from integration-free iPS cells and their cell biological characterization. Stem Cell Res Ther 8:217
Williams, D S; Chadha, A; Hazim, R et al. (2017) Gene therapy approaches for prevention of retinal degeneration in Usher syndrome. Gene Ther 24:68-71
Orme, Mariam H; Liccardi, Gianmaria; Moderau, Nina et al. (2016) The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles. Nat Commun 7:10972
Goldberg, Andrew F X; Moritz, Orson L; Williams, David S (2016) Molecular basis for photoreceptor outer segment architecture. Prog Retin Eye Res 55:52-81
Eblimit, Aiden; Nguyen, Thanh-Minh T; Chen, Yiyun et al. (2015) Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina. Hum Mol Genet 24:1584-601
Jiang, Mei; Esteve-Rudd, Julian; Lopes, Vanda S et al. (2015) Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis. J Cell Biol 210:595-611
Volland, Stefanie; Hughes, Louise C; Kong, Christina et al. (2015) Three-dimensional organization of nascent rod outer segment disk membranes. Proc Natl Acad Sci U S A 112:14870-5

Showing the most recent 10 out of 27 publications