KINESIN IN PHOTORECEPTOR CELLS

描述（由申请人提供）：本项目的长期总体目标 研究是为了帮助理解细胞机制， 感光细胞，特别是那些参与周转的细胞。 光传导膜和重要的感光细胞的活力。的 提出的计划是重点了解驱动蛋白II的作用， 感光细胞在构成本提案基础的一项研究中， 我们研究了小鼠的感光细胞， KIF 3a基因是驱动蛋白II的一种专性运动亚基。（驱动蛋白II） 由异源三聚体组成，具有两个运动亚基和一个辅助蛋白。 使用cre-lox系统，用转基因小鼠实现选择性敲除 携带由IRBP启动子驱动的cre。本研究证明 驱动蛋白II是成熟的细胞内蛋白质正常转运所必需的。 光感受器细胞，并且是光感受器细胞活力所必需的。 在拟议的研究中，我们的目标是测试从这项研究中产生的假设， 关于驱动蛋白II在蛋白质运输和光感受器中的作用 细胞退化 我们将测试是否有编码驱动蛋白II亚基的基因可以 导致遗传性感光细胞退化。我们将探讨 光感受器驱动蛋白II的分子间相互作用 蛋白质-蛋白质相互作用的研究表明，从我们的敲除研究迄今为止。我们 将改进我们现有的选择性敲除光感受器的方法 KIF 3a通过产生一种更有效的方式来提供cre， 几乎所有的光感受器都能同时被移除。我们将使用这个 改进的方法来测试关于驱动蛋白II功能的不同假设 感光细胞最后，我们将测试arrestin绑定的重要性 磷酸化视紫红质在感光细胞死亡中的作用 这项拟议中的研究与蛋白质如何传递的奥秘有关 感光细胞的外节， 驱动蛋白和光感受器变性。光感受器退化， 是由各种不同基因的突变引起的（许多还没有被发现）。 （已识别），是人类失明的主要原因。

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.