Although the rapid transport of neuronal organelles has been intensively studied using in vitro cell models, virtually nothing is known about how this phenomenon is controlled and coordinated in intact cells. One major aim of this study is to determine whether rapid organelle transport is modulated to deliver specific classes of organelles to regions of the neuron where they are needed. Using primary cultured chick neurons maintained in a culture system in which their elongation can be controlled, quantitative measurements of organelle transport will made to determine movement is coordinated with growth. The second major aim is to address how the direction of organelle movement is controlled, using conditions that influence the direction of transport in non-neuronal cells to probe intact and permeabilized neurons in culture. The third major aim of this study is to determine what role the mechanochemical ATPase kinesin plays in bidirectional rapid organelle transport. Specific antibodies directed against this enzyme will be introduced into cultured neurons in an effort to disrupt movement of a class of bidirectionally-transported organelles. Because it provides a metabolic link between the periphery of neurons and the site of synthesis in the cell body, rapid axonal transport is essential for the development and maintenance of all nerves; thus, the insight into its mechanism gained by the proposed research can be expected to contribute to our understanding of the development, defects, and diseases of the nervous system. In addition, since neuronal organelle transport must share many features in common with organelle traffic in other cell types, information acquired in this system should provide insight into many other systems of intracellular motility.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 2 (NEUB)
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Harvard University
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