Microtubule Motors and Chemosensory Behavior

描述（由申请人提供）：神经元是高度极化的细胞，专门用于神经系统中的信息处理，并依赖于基于微管（MT）的运输系统进行组装，维护和功能。例如，秀丽隐杆线虫（Caenorhabditis elegans）的化学感觉神经元是双极性细胞，它们利用纤毛树突探测环境中的化学物质（如细菌食物释放的化学引诱剂），并通过轴突传递信号来协调适当的运动反应（如向化学引诱剂的来源移动）。我们假设这些化学感觉神经元上的树突和感觉纤毛的形成和功能依赖于两种异质运动蛋白（异三聚体运动蛋白-1和二聚体运动蛋白-3）驱动的基于mt的树突内和纤毛内运输，而神经传递依赖于部分由单体运动蛋白Unc-104驱动的轴突运输。为了验证这一假设，具体目标是：

DESCRIPTION (provided by applicant): Neurons are highly polarized cells that are specialized for information processing in the nervous system and depend upon microtubule (MT)- based transport systems for their assembly, maintenance and function. For example, chemosensory neurons in the nematode, Caenorhabditis elegans, are bipolar cells that use ciliated dendrites to detect chemicals in the environment (e.g. chemoattractants released by their bacterial food) and that transmit signals from their axons to coordinate the appropriate motile response (e.g. movement towards the source of the chemoattractant). We hypothesize that the formation and function of dendrites and sensory cilia on these chemosensory neurons depend upon MT-based intradendritic and intraciliary transport driven by two heteromeric kinesins, heterotrimeric kinesin-ll and dimeric Osm-3, whereas neurotransmission depends upon axonal transport driven, in part, by the monomeric kinesin, Unc-104. To test this hypothesis, the specific aims are: 1. To use EM and an in vivo transport assay to characterize the basic transport apparatus (i.e. motors, MT tracks and transport rafts/vesicles) operating in chemosensory neurons. 2. To dissect the functional relationships between the kinesin-Il and Osm-3 transport pathways in the formation and function of dendrites and sensory cilia. 3. To dissect the roles of Unc-104 in the binding and axonal transport of synaptic vesicles. 4. To study the relationship between intraciliary transport and chemosensory behavior of the adult C. elegans. Collectively, these studies will improve our understanding of the role of MT-based transport in the formation and function of neurons and in the control of the behavior of a primitive metazoan.