The Journal of Neuroscience, April 27, 2005, ():
Protein-Protein Coupling/Uncoupling Enables Dopamine D2 Receptor Regulation of AMPA Receptor-Mediated Excitotoxicity
J. Neurosci. Zou et al.
25: 4385
Supplemental data
Files in this Data Supplement:
- Figure A
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Figure A. Kainate-induced neurotoxicity of dissociated primary cultures of hippocampal neurons. Pretreatment with 10 然 quinpirole reduced the apoptosis induced by 300 and 500 然 kainate (coincubation of 10 ?M MK-801 and 2 ?M nimodipine). Quantification of kainate-induced toxicity of rat hippocampal neurons through PI fluorescence measurements show a reduction in toxicity after quinpirole pretreatment, an effect that was more pronounced with 500 然 kainate. Data were analyzed by t-test. *, significantly different from the 300 然 kainate group (P<0.05, n=3). **, significantly different from the 500 然 kainate group (P<0.01, n=3).
- Figure B
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Figure B. Illustration of the D2Long mini-genes/fusion proteins used in this study. The various mini-genes/fusion protein constructs are depicted with their respective initial and terminal amino acids. (IL3: Intracellular Third Loop; CT: Carboxyl Terminus).
- Figure C
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Figure C. Confirmation of an interaction between NSF and D2 receptor in the absence of AMPA receptors. In HEK-293T cells transfected with the D2Long receptor only, anti-NSF Western blots of D2 receptor antibody immunoprecipitates run on SDS-PAGE, reveal that the D2 receptor can co-precipitate endogenous NSF in the absence of the AMPA receptor subunits, GluR1 and GluR2 (top panel). Western blot reveals that Cos-7 cells also express endogenous NSF protein (lower panel).
- Figure D
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Figure D. Illustration of a proposed model for the D2 receptor regulated rescue from AMPA-induced cell death. One mechanism that could allow for this D2 receptor regulated rescue could be mediated by NSF. With NSF shuttling between GluR2 and the D2 receptor, the GluR2 subunit becomes accessible and p85 is recruited to the GluR2 subunit. This subsequently results is PI3K activation and activation of anti-apoptotic pathways.
