Molekulare und funktionelle Charakterisierung molekularer Motoren sensorischer Zellen

感觉细胞分子马达的分子和功能表征

• 批准号: 5242518
• 负责人: Professor Dr. Uwe Wolfrum
• 金额: --
• 依托单位: Institut für Molekulare Physiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2003-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5242518?language=en
• 关键词: Molekulare; und; funktionelle; Charakterisierung; molekularer

Sensory cells are commonly highly polarized and highly active neurons which are divided into anatomic and functional distinct compartments. Efficient vectorial transport systems are necessary to deliver molecules between the compartments. We have previously identified two distinct intracellular transport systems which mediate rhodopsin trafficking in vertebrate photoreceptor cells. In the inner segment, post-Golgi vesicles are translocated along microtubules by cytoplasmic dynein to the apical inner segment membrane at the base of the connecting cilium which gives the joint between the inner and the outer segment. Representing a novel mechanism, the dynein light chain Tctex-1 binds to rhodopsin as an integral membrane receptor anchoring the vesicle cargo at the transport motor. In a final step, the unconventional myosin VIIa surprisingly mediates rhodopsin delivery in the ciliary membrane to nascent outer segment disks. In the present proposal, we will investigate both actin-based and microtubule-based transport mechanisms in specialized sensory cells with a focus on regulation of both motile systems as well as a special future interest in the processes of the hand-over of the cargo between both systems. Our investigations will provide important novel insights into the role of motor proteins in the vectorial transport cells, especially in sensory cells, and will shed light on the molecular basis of human sensory degeneration diseases.

感觉细胞通常是高度极化和高度活跃的神经元，分为解剖学和功能上不同的区室。有效的矢量运输系统对于在隔室之间传递分子是必要的。我们之前已经确定了两种不同的细胞内转运系统，它们介导脊椎动物感光细胞中的视紫红质运输。在内节中，高尔基后囊泡通过细胞质动力蛋白沿着微管移位到连接纤毛基部的顶端内节膜，该纤毛提供了内节和外节之间的接合处。动力蛋白轻链 Tctex-1 代表一种新颖的机制，作为一种完整的膜受体与视紫红质结合，将囊泡货物锚定在运输马达上。在最后一步中，非常规肌球蛋白 VIIa 令人惊讶地介导视紫红质在睫状膜中递送至新生的外节盘。在本提案中，我们将研究专门感觉细胞中基于肌动蛋白和基于微管的运输机制，重点关注两个运动系统的调节，以及对两个系统之间货物移交过程的特殊未来兴趣。我们的研究将为运动蛋白在矢量运输细胞（尤其是感觉细胞）中的作用提供重要的新见解，并将揭示人类感觉退化疾病的分子基础。