Year: 2011
Type: dissertation
Abstract: NMDA-type glutamate receptors (NMDAR) regulate neurotransmission and excitotoxicity. NMDAR signaling is believed to be dependent on NR2 subunit (A-D) composition and interactions with intracellular proteins. To determine the role of individual NR2 subunits in NMDAR signaling, I examined the biochemical interactions and colocalization of NR2A and NR2B NMDAR subunits with PSD-95 and CaMKII. Immunofluorescent colocalization revealed that by perturbing PSD-95 PDZ interactions using a targeted peptide (TAT-NR2B9c) increased association of PSD-95 with NR2A and CaMKII with NR2B; furthermore, decreases in association of CaMKII with NR2A and PSD-95 with NR2B were observed. The effects of TAT-NR2B9c were dependent upon NMDAR stimulation with 10μM NMDA and were not observed in untreated cells or at toxic doses of NMDA (40 μM). Thus, disrupting PSD-95 PDZ interactions produced activity-dependent differences in the co-localization of NR2A and NR2B with key signaling proteins, providing evidence that individual NR2 subunits may confer differential signaling to NMDARs.
Source: TSpace (University of Toronto)
Author: Kevin Sam
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2755747623