This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Keywords: membrane traffic, vesicular monoamine, neurotransmitter storage Abstract: Synaptic transmission depends on the efficient packaging of neurotrasnmitters into specialized secretory vesicles. For monoamines that are synthesized in the cytoplasm, this package requires active transport across the vesicle membrane. Whereas the specific transport activity definies the content of secretory vesicles, the localization of the transport protein on distinct vesicles will determine the mode and site of monoamine release. The long-term objective of this proposal is to understand how changes in neurotransmitter storage and release influence synaptic transmission, and hence behavior. The strategy is to study the sorting of the transport proteins that package monoamines into distrinct secretory vesicles. Using PC12 cells as a model system, we have found that vesicular monoaminie transporters perferentially localize to LDCVs whereas the close related vesicular acetylcholine transporter perferentially to SVs. We will focus on on neuronal VMAT2 in this proposal to explore the mechanisms involved in the sorting of VMAT2 to LDCVs with the follwoing Specific Aims: 1) to examine the routes by which VMAT2 sorts to secretory vesicles. 2) to identify the sorting sequences that target VMAT2 to LDCVs 3) to identify interacting proteins that regulate VMAT2 sorting.
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