Molekulare und funktionelle Charakterisierung molekularer Motoren sensorischer Zellen

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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.