Neuroscience 2004 Abstract
| Presentation Number: | 843.11 |
|---|---|
| Abstract Title: | Characterization of a new NMDAR-regulated gene affecting neuronal activity. |
| Authors: |
Tu, S.*1
; Shin, Y.1
; States, B.1
; Tong, G.1
; Lipton, S. A.1
; Nobuki, N.1
1Ctr Neurosci & Aging, The Burnham Inst, La Jolla, CA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Ligand Gated Ion Channels -- Glutamate receptors: NMDA receptors |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Synaptic Transmission<br />-- Postsynaptic mechanisms: Excitatory |
| Session: |
843. NMDA Receptors IV Poster |
| Presentation Time: | Wednesday, October 27, 2004 10:00 AM-11:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # G25 |
| Keywords: | PSD-95, PDZ, NR3A, Knockout |
NMDA receptors (NMDARs) are composed of NR1, NR2, and NR3 subunits. We previously identified p16 as a protein whose expression is upregulated in the NR3A KO brain compared to WT. Interestingly, forced expression of p16 in cultured cortical and hippocampal neurons results in an increase in NMDA-evoked currents, but not in AMPA- or GABA-evoked currents (Tu et al., 2003, SfN abstract 796.2). Since proteins that modulate NMDAR activity are often directly or indirectly associated with the NMDAR, we decided to examine this possibility. Based on the analysis of protein motifs using the Scansite 2.0 program (Obenauer et al., 2003), the C-terminal end of p16 was predicted to bind class I PDZ domains. We thus hypothesized that p16 might interact with PSD-95, which binds to NR2 and contains PDZ domains. We co-expressed p16-EGFP (a fusion protein of p16 and EGFP) and PSD-95 in COS-7 cells, and performed co-immunoprecipitation experiments. The experiments showed that these two proteins associate each other in these cells. Next, we expressed p16-EGFP in cultured neurons and examined its subcellular localization relative to those of PSD-95. Immunohistochemistry revealed that p16-EGFP localized to dendrites either with or adjacent to PSD-95. Taken together, these results suggest that p16 physically interacts with PSD-95, and this interaction may mediate the effect of p16 on NMDAR activity. Finally, we recently discovered that there are variants of p16 that are expressed in the brain. Some of these variants do not bind to PSD-95 and may act as dominant negative forms of p16. Hence, the regulation of NMDAR activity by these proteins is potentially complex.
Supported by NIH P01 HD29587 and R01 EY05477
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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