Publication Date:
1999-06-12
Description:
The efficiency with which N-methyl-D-aspartate receptors (NMDARs) trigger intracellular signaling pathways governs neuronal plasticity, development, senescence, and disease. In cultured cortical neurons, suppressing the expression of the NMDAR scaffolding protein PSD-95 (postsynaptic density-95) selectively attenuated excitotoxicity triggered via NMDARs, but not by other glutamate or calcium ion (Ca2+) channels. NMDAR function was unaffected, because receptor expression, NMDA currents, and 45Ca2+ loading were unchanged. Suppressing PSD-95 blocked Ca2+-activated nitric oxide production by NMDARs selectively, without affecting neuronal nitric oxide synthase expression or function. Thus, PSD-95 is required for efficient coupling of NMDAR activity to nitric oxide toxicity, and imparts specificity to excitotoxic Ca2+ signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sattler, R -- Xiong, Z -- Lu, W Y -- Hafner, M -- MacDonald, J F -- Tymianski, M -- NS 39060/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Jun 11;284(5421):1845-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Toronto Western Hospital, University of Toronto, Lab 11-416, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10364559" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/*metabolism
;
Calcium Channels/metabolism
;
Cell Survival
;
Cells, Cultured
;
Enzyme Activation
;
Guanylate Kinase
;
Intracellular Signaling Peptides and Proteins
;
Membrane Proteins
;
Mice
;
N-Methylaspartate/toxicity
;
Nerve Tissue Proteins/genetics/*metabolism
;
Neurons/cytology/*metabolism
;
Nitric Oxide/*metabolism
;
Nitric Oxide Synthase/metabolism
;
Nitric Oxide Synthase Type I
;
Nucleoside-Phosphate Kinase/metabolism
;
Oligodeoxyribonucleotides, Antisense
;
Patch-Clamp Techniques
;
Receptors, N-Methyl-D-Aspartate/*metabolism
;
Second Messenger Systems
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
