The long-term objective of this proposal is to gain insight into the molecular mechanisms involved in the clustering and postsynaptic targeting of type A receptors for y-aminobutyric acid (GABAA), the principal receptors that mediate neural inhibition in the mammalian CNS. The y2 subunit of GABAA receptors is essential for clustering and postsynaptic targeting of these receptors and gephyrin in vivo during development. However, it is not known whether the y2 subunit is required for maintenance of GABAA receptors and gephyrin at mature synapses. The first main objective is to determine whether the y2 subunit is required for maintenance of GABAA receptors and gephyrin at mature synapses, after synaptic localization of GABAA receptors has been established. To address this question, we will take advantage of mice that carry a conditional mutation in the y2 subunit gene that can be induced by Cre/loxP recombination. In particular, we will test whether the y2 subunit is still required for clustering after synaptic localization of GABAA receptors has been established. The second main objective is to identify and isolate novel factors that interact with GABAA receptor subunits and promote receptor clustering and targeting to specific postsynaptic sites. It is predicted that the differential subcellular distribution of GABAA receptor isoforms require specific factors to allow the discrimination of GABAA receptors with different subunit composition. Various fragments derived from several GABAA receptor subunits and gephyrin will be used as molecular probes to screen protein expression libraries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS011070-02
Application #
6539535
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (01))
Program Officer
Stewart, Randall
Project Start
2002-05-15
Project End
Budget Start
2002-05-15
Budget End
2003-05-14
Support Year
2
Fiscal Year
2002
Total Cost
$46,192
Indirect Cost
Name
Pennsylvania State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802