Requirement of JIP scaffold proteins for NMDA-mediated signal transduction
- Norman J. Kennedy1,
- Gilles Martin2,
- Anka G. Ehrhardt1,
- Julie Cavanagh-Kyros1,
- Chia-Yi Kuan3,
- Pasko Rakic4,
- Richard A. Flavell5,
- Steven N. Treistman2, and
- Roger J. Davis1,6
- 1 Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 2 Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 3 Division of Developmental Biology, Cincinnati Children’s Hospital Research Foundation, Cincinnati, Ohio 45229, USA;
- 4 Department of Neurobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut 06520, USA;
- 5 Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut 06520, USA
Abstract
JIP scaffold proteins are implicated in the regulation of protein kinase signal transduction pathways. To test the physiological role of these scaffold proteins, we examined the phenotype of compound mutant mice that lack expression of JIP proteins. These mice were found to exhibit severe defects in N-methyl-D-aspartic acid (NMDA) receptor function, including decreased NMDA-evoked current amplitude, cytoplasmic Ca++, and gene expression. The decreased NMDA receptor activity in JIP-deficient neurons is associated with reduced tyrosine phosphorylation of NR2 subunits of the NMDA receptor. JIP complexes interact with the SH2 domain of cFyn and may therefore promote tyrosine phosphorylation and activity of the NMDA receptor. We conclude that JIP scaffold proteins are critically required for normal NMDA receptor function.
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Footnotes
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↵6 Corresponding author.
↵6 E-MAIL Roger.Davis{at}Umassmed.Edu; FAX (508) 856-3210.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1563107
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- Received April 19, 2007.
- Accepted July 24, 2007.
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Freely available online through the Genes & Development Open Access option.
- Copyright © 2007, Cold Spring Harbor Laboratory Press
