| NSF Org: |
IOS Division Of Integrative Organismal Systems |
| Recipient: |
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| Initial Amendment Date: | August 20, 1999 |
| Latest Amendment Date: | December 5, 2000 |
| Award Number: | 9974517 |
| Award Instrument: | Continuing Grant |
| Program Manager: |
Soo-Siang Lim
slim@nsf.gov (703)292-7878 IOS Division Of Integrative Organismal Systems BIO Directorate for Biological Sciences |
| Start Date: | September 1, 1999 |
| End Date: | September 30, 2001 (Estimated) |
| Total Intended Award Amount: | $344,524.00 |
| Total Awarded Amount to Date: | $344,524.00 |
| Funds Obligated to Date: |
FY 2000 = $109,394.00 FY 2001 = $112,697.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
5700 CASS AVE STE 4900 DETROIT MI US 48202-3692 (313)577-2424 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
5700 CASS AVE STE 4900 DETROIT MI US 48202-3692 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | NEURONAL AND GLIAL MECHANISMS |
| Primary Program Source: |
app-0101 app-0199 |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
Proposal #9974517
Lisa Elferink
Synaptic transmission is the primary form of communication between neurons. It is a highly regulated process that underlies virtually all neuronalpathways, from simple reflexes to higher order brain function such as learning and memory. Synaptic transmission involves the release of neurotransmitters from synaptic and secretory vesicles by exocytosis followed by the retrieval of vesicle membranes by endocytosis. Therefore endocytosis is essential for the continued secretory function of neural cells. Impairment of this process is likely to result in paralysis or mental disorders. The long term goal of this proposal is to examine the molecular mechanism mediating secretory vesicle recycling and its role in synaptic transmission. Rab GTPases are a family of monomeric proteins involved in membrane transport. Rab15 will form a focal point for these studies since its expression is enriched over other endosomal rabs in cells with high levels of secretion such as neurons and neuroendocrine cells. Moreover, rab15 localizes to early endosomes in non-neuronal cells, consistent with its proposed role in endocytosis. This proposal describes experiments that examine the role of rab15 in secretory vesicle recycling. First we will identify the endocytic transport step regulated by rab15 in non-neuronal cells - key findings will be applied to neuroendocrine cells.
Second, we will determine rab15's subcellular localization in neuroendocrine cells. Finally, we will examine the role of rab15 in secretory vesicle recycling. Together, these studies will shed new light
on the role of rab15 in regulating the recycling of secretory vesicles during synaptic transmission and more generally, on the molecular mechanisms determining the specificity of endocytosis in all cell types.
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