A Genetic Analysis of Axonal Transport in Synaptogenesis

描述（由申请人提供）：对于新突触的组装，生长的轴突需要用于稳定早期接触、转化轴突形态以及在两个细胞之间建立功能连接的分子。这些分子在细胞体中合成，必须沿着轴突运输。事实上，突触构件的运输对于突触发生至关重要，并且可能受到密切调控。它也可能对修改成人大脑中的突触至关重要。 因此，我们可能最终了解突触发生中马达的特异性和调节，我们建议使用果蝇遗传学来检查这些组件是如何被运送到轴突中的。该项目的起点是一种新发现的突变，即完美连接（Imac），其中生长锥似乎可以正确地导航到它们的目标，但突触不会形成。突触发生的过程被阻断了。该基因编码驱动蛋白马达。该提案假设，这种电机是需要运输材料的突触，它是不同于电机或电机所需的神经突生长和导航。该提议的目的是：1）表征突变体中轴突-靶相互作用以确定需要Imac的程度; 2）确定其转运依赖于Imac的特定突触分子，并研究Imac与这些货物偶联的方式; 3）将其他驱动蛋白的功能与Imac的功能相关联。从这些实验中，我们希望推进我们的长期目标，阐明突触形成的机制。

DESCRIPTION (provided by applicant): For the assembly of a new synapse, the growing axon requires molecules for stabilizing early contacts, transforming the morphology of the axon, and building a functional connection between the two cells. These molecules are synthesized in the cell body and must be transported down the axon. Indeed, the transport of synaptic building blocks is crucial to synaptogenesis and is likely to be closely regulated. It is also likely to be crucial to modifying synapses in the adult brain. So that we may ultimately understand the specificity and regulation of the motors in synaptogenesis, we propose to use Drosophila genetics to examine how those components are transported into the axon. The starting point of the project is a newly discovered mutation, immaculate connections (Imac) in which growth cones appear to navigate correctly to their targets, but synapses do not form. The process of synaptogenesis is blocked. This gene encodes a kinesin motor. The proposal hypothesizes that this motor is required for the transport of materials for synaptogenesis and that it is distinct from the motor or motors that are required for neurite outgrowth and navigation. The aims of this proposal are: 1) to characterize the axon-target interactions in the mutant to determine the extent to which Imac is required; 2) to determine specific synaptic molecules whose transport is dependent on Imac and to investigate the manner in which Imac couples to those cargos; 3) to relate the function of other kinesins to that of Imac. From these experiments, we hope to advance our long term goal of elucidating the mechanism by which synapses form.