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.
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