): The central idea of this project is that microtubule based motility in photoreceptors is essential for formation and maintenance of the outer segment. The application is based on two new discoveries in my laboratory. First, two cytoplasmic dynein heavy chains are expressed in photoreceptor inner segments and a subset of the dynein localizes to the basal body/cilium complex and outer segment. Second, mammalian homologues of """"""""raft"""""""" proteins known to form transport complexes in cilia and flagella are also found associated with the basal body/cilium complex in photoreceptors. We hypothesize that cytoplasmic dynein plays multiple roles in trafficking to support the outer segment. In the cilium and outer segment we propose that cytoplasmic dynein and """"""""raft"""""""" proteins are part of a bidirectional transport system similar to """"""""intraflagellar transport"""""""" in cilia and flagella and referred to here as """"""""intersegmental transport."""""""" Cytoplasmic dynein would serve as a retrograde motor for movement from outer to inner segment while kinesin would serve as an anterograde motor. In the inner segment, we hypothesize that cytoplasmic dynein is critical for the organization of membrane compartments and trafficking to the outer segment. In order to understand the multiple roles of cytoplasmic dynein in photoreceptors we will (1) characterize the molecular form(s) and localization of cytoplasmic dynein, (2) isolate and characterize the protein components of the hypothetical intersegmental rafts, and (3) use targeted expression of transgenes in rod cells in Xenopus to study the function of cytoplasmic dynein and raft proteins in early photoreceptor development.
| Lewis, Tylor R; Kundinger, Sean R; Link, Brian A et al. (2018) Kif17 phosphorylation regulates photoreceptor outer segment turnover. BMC Cell Biol 19:25 |
| Lewis, Tylor R; Zareba, Mariusz; Link, Brian A et al. (2018) Cone myoid elongation involves unidirectional microtubule movement mediated by dynein-1. Mol Biol Cell 29:180-190 |
| Lewis, Tylor R; Kundinger, Sean R; Pavlovich, Amira L et al. (2017) Cos2/Kif7 and Osm-3/Kif17 regulate onset of outer segment development in zebrafish photoreceptors through distinct mechanisms. Dev Biol 425:176-190 |
| Collery, Ross F; Volberding, Peter J; Bostrom, Jonathan R et al. (2016) Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages. Invest Ophthalmol Vis Sci 57:6805-6814 |
| Besharse, Joseph C; McMahon, Douglas G (2016) The Retina and Other Light-sensitive Ocular Clocks. J Biol Rhythms 31:223-43 |
| Miesfeld, Joel B; Gestri, Gaia; Clark, Brian S et al. (2015) Yap and Taz regulate retinal pigment epithelial cell fate. Development 142:3021-32 |
| Fogerty, Joseph; Besharse, Joseph C (2014) Subretinal infiltration of monocyte derived cells and complement misregulation in mice with AMD-like pathology. Adv Exp Med Biol 801:355-63 |
| Bader, Jason R; Kusik, Brandon W; Besharse, Joseph C (2012) Analysis of KIF17 distal tip trafficking in zebrafish cone photoreceptors. Vision Res 75:37-43 |
| Wong-Riley, Margaret T T; Besharse, Joseph C (2012) The kinesin superfamily protein KIF17: one protein with many functions. Biomol Concepts 3:267-282 |
| Malicki, Jarema; Besharse, Joseph C (2012) Kinesin-2 family motors in the unusual photoreceptor cilium. Vision Res 75:33-6 |
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