Ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the vertebrate nervous system. Changes in the properties of glutamate receptor subunits has been implicated in such disease states as epilepsy schizophrenia, and in excitotoxic cell death following transient ischemia, which occurs in stroke. Heteromultimerization of glutamate receptor subunits determines critical receptor properties such as calcium permeability, current amplitude, and current-voltage characterization. Subunit oligomerization, however, occurs only within certain glutamate receptor subfamilies, suggesting the existence of a protein domain conferring subunit specificity on the assembly process. The long-range objective of these experiments is to define the molecular mechanisms that determine oligomerization of glutamate receptor subunits.
Specific Aim #1 applies a biochemical approach to define and characterize regions of the GluR1 subunit involved in subunit associations. Experiments in Specific Aim #2 evaluate the roles of such protein domains in the assembly process using electrophysiological analyses. Such experiments will identify regions necessary for subunit oligomerization. In order to confirm these protein domains are sufficient to promote assembly, chimeric channels will be constructed in Specific Aim #3 and tested for their ability to associate with subunits from another subfamily. Finally, Specific Aim 34 proposes experiments to explore the kinetics and relative affinities of subunit interactions using biomolecular interaction analyses.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019345-02
Application #
2910035
Study Section
Special Emphasis Panel (ZRG1-NLS-1 (01))
Project Start
1999-05-01
Project End
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037