Molekulare und funktionelle Charakterisierung molekularer Motoren sensorischer Zellen

感觉细胞通常是高度极化和高度活跃的神经元，分为解剖和功能不同的室。有效的矢量运输系统是在隔室之间运送分子所必需的。我们以前已经确定了两种不同的细胞内运输系统介导视紫红质运输在脊椎动物感光细胞。在内节段，高尔基后囊泡通过细胞质动力蛋白沿微管转移到连接纤毛基部的顶端内节膜，从而形成内外节段之间的连接。动力蛋白轻链Tctex-1作为一个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，这代表了一种新的机制。在最后一步中，非常规的肌球蛋白VIIa出人意料地介导了睫状膜上视紫红质向新生的外节盘的传递。在目前的建议中，我们将研究基于肌动蛋白和基于微管的运输机制在特殊的感觉细胞中，重点关注这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载体运输细胞，特别是在感觉细胞中的作用提供重要的新见解，并将揭示人类感觉变性疾病的分子基础。

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.