How does a single neuron establish and maintain many functionally distinct synapses? How are specific synaptic proteins added and removed from specific synapses to regulate signal transmission efficiency? Recent evidence suggests that changes in post-synaptic protein distribution constitute a cell biological mechanism leading to long term potentiation and long term depression, which are believed to form the basis of memory and learning. It was previously shown that a phylogenetically conserved PDZ-domain containing protein (LIN-10) is required for targeting of an AMPA-type glutamate receptor (GluR) to central synapses in C. elegans. This synaptic function of LIN- 10 is likely to be phylogenetically conserved since a human orthologue (X11/Mint) can functionally replace the endogenous worm protein. The goal of this proposal is to elucidate the mechanism by which LIN-10 regulates the abundance of GluR localization at post-synaptic elements as a step towards understanding the dynamic regulation of synaptic protein localization. A comparison with the function of LIN-10 in epithelial cells will test the hypothesis that a basic mechanism for protein localization is common in both cell types.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS041705-05
Application #
6753528
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (20))
Program Officer
Tagle, Danilo A
Project Start
2002-06-01
Project End
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
5
Fiscal Year
2004
Total Cost
$50,548
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199