The broad goals for this proposal are to identify subunit-specific N- methyl-D-aspartate (NMDA) receptor interacting proteins, and then to characterize the functional consequences of identified interactions. This project has the potential to further elucidate specific signaling events that may be involved in the regulation of synaptic plasticity, and may describe the identification of novel molecular events involved in NMDA receptor regulation and anchoring. Interacting proteins will initially be identified through the use of the yeast two-hybrid system to screen rat brain cDNA libraries utilizing various NMDA receptor cytoplasmic carboxy-termini as """"""""bait"""""""" constructs. Following fundamental characterization of interactions utilizing heterologous cell systems and biochemical assays, the consequences of interaction on localization will be assayed in actual neuronal systems. This will be accomplished by recombinant adenovirus mediated infection of primary cultured cortical neurons. Analysis will include characterizing altered localization patterns of endogenous receptors in the presence of overexpressed interacting proteins and selected regions of mutated NMDA receptors that may exert dominant-negative effects on localization. Additionally, the localization pattern of introduced NMDA receptors that have mutated interaction domains will also be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH012248-01
Application #
2775486
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (02))
Program Officer
Goldschmidts, Walter L
Project Start
1999-06-15
Project End
Budget Start
1999-06-15
Budget End
2000-06-14
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218