KINESIN IN PHOTORECEPTOR CELLS

感光细胞中的驱动蛋白

• 批准号: 6654910
• 负责人: DAVID S WILLIAMS
• 金额: $ 27.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6654910
• 关键词: arrestins; gene expression; gene mutation; gene targeting; genetically modified animals; kinesin; laboratory mouse; protein binding; protein protein interaction; protein structure function; protein transport; retina degeneration; rhodopsin; uvea ciliary body; visual photoreceptor; visual phototransduction

DESCRIPTION (provided by applicant): The long-term overall goal of this research is to help in the understanding of cellular mechanisms in photoreceptor cells, especially those involved in turnover of the phototransductive membrane and important for photoreceptor cell viability. The proposed plan is to focus on understanding the role of kinesin II in photoreceptor cells. In a study that forms the basis for the present proposal, we studied photoreceptor cells in mice with photoreceptor-specific knock-out of the gene for KIF3a, an obligatory motor subunit of kinesin II. (Kinesin II consists of a heterotrimer, with two motor subunits and an accessory protein.) Selective knock-out was achieved using the cre-lox system, with transgenic mice carrying cre that was driven by the IRBP promoter. This study demonstrated that kinesin II is required for normal transport of proteins within mature photoreceptor cells and is essential for photoreceptor cell viability. In the proposed research, we aim to test hypotheses generated from this study, concerning the roles of kinesin II in protein transport and in photoreceptor cell degeneration. We will test whether any of the genes encoding the subunits of kinesin II could be responsible for inherited photoreceptor cell degeneration. We will explore the molecular interactions of photoreceptor kinesin II by testing protein-protein interactions suggested from our knock-out studies thus far. We will improve upon our current method of selective knock-out of photoreceptor KIF3a by generating a more effective way to deliver cre, so that ideally KIF3a can be removed in nearly all photoreceptors at the same time. We will use this improved method to test different hypotheses about kinesin II function in photoreceptor cells. Finally, we will test the importance of arrestin-bound phosphorylated rhodopsin in photoreceptor cell death. The proposed research is pertinent to the mystery of how proteins are delivered to the outer segment of photoreceptor cells, to the general function of kinesins, and to photoreceptor degeneration. Photoreceptor degeneration, which is caused by mutations in a variety of different genes (many yet to be identified), is a major cause of human blindness.

描述（由申请人提供）：该项目的长期总体目标