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A Genetic Analysis of Axonal Transport in Synaptogenesis


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.


Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.