Dexras1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON

被引:272
作者
Fang, M
Jaffrey, SR
Sawa, A
Ye, KQ
Luo, XJ
Snyder, SH [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0896-6273(00)00095-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Because nitric oxide (NO) is a highly reactive signaling molecule, chemical inactivation by reaction with oxygen, superoxide, and glutathione competes with specific interactions with target proteins. NO signaling may be enhanced by adaptor proteins that couple neuronal NO synthase (nNOS) to specific target proteins. Here we identify a selective interaction of the nNOS adaptor protein CAPON with Dexras1, a brain-enriched member of the Pas family of small monomeric G proteins. We find that Dexras1 is activated by NO donors as well as by NMDA receptor-stimulated NO synthesis in cortical neurons. The importance of Dexras1 as a physiologic target of nNOS is established by the selective decrease of Dexras1 activation, but not H-Ras or four other Pas family members, in the brains of mice harboring a targeted genomic deletion of nNOS (nNOS(-/-)). We also find that nNOS, CAPON, and Dexras1 form a ternary complex that enhances the ability of nNOS to activate Dexras1. These findings identity Dexras1 as a novel physiologic NO effector and suggest that anchoring of nNOS to specific targets is a mechanism by which NO signaling is enhanced.
引用
收藏
页码:183 / 193
页数:11
相关论文
共 48 条
[1]  
Borjigin J, 1999, J NEUROSCI, V19, P1018
[2]   NITRIC-OXIDE MEDIATES GLUTAMATE-LINKED ENHANCEMENT OF CGMP LEVELS IN THE CEREBELLUM [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :9030-9033
[3]   TRANSIENT NITRIC-OXIDE SYNTHASE NEURONS IN EMBRYONIC CEREBRAL CORTICAL PLATE, SENSORY GANGLIA, AND OLFACTORY EPITHELIUM [J].
BREDT, DS ;
SNYDER, SH .
NEURON, 1994, 13 (02) :301-313
[4]   ISOLATION OF NITRIC-OXIDE SYNTHETASE, A CALMODULIN-REQUIRING ENZYME [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (02) :682-685
[5]   Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains [J].
Brenman, JE ;
Chao, DS ;
Gee, SH ;
McGee, AW ;
Craven, SE ;
Santillano, DR ;
Wu, ZQ ;
Huang, F ;
Xia, HH ;
Peters, MF ;
Froehner, SC ;
Bredt, DS .
CELL, 1996, 84 (05) :757-767
[6]   Numb-associated kinase interacts with the phosphotyrosine binding domain of numb and antagonizes the function of numb in vivo [J].
Chien, CT ;
Wang, SW ;
Rothenberg, M ;
Jan, LY ;
Jan, YN .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (01) :598-607
[7]   THE RAT-BRAIN POSTSYNAPTIC DENSITY FRACTION CONTAINS A HOMOLOG OF THE DROSOPHILA DISKS-LARGE TUMOR SUPPRESSOR PROTEIN [J].
CHO, KO ;
HUNT, CA ;
KENNEDY, MB .
NEURON, 1992, 9 (05) :929-942
[8]   Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation [J].
Choi, YB ;
Tenneti, L ;
Le, DA ;
Ortiz, J ;
Bai, G ;
Chen, HSV ;
Lipton, SA .
NATURE NEUROSCIENCE, 2000, 3 (01) :15-21
[9]   AKAPs: from structure to function [J].
Colledge, M ;
Scott, JD .
TRENDS IN CELL BIOLOGY, 1999, 9 (06) :216-221
[10]  
Curtis J, 1999, J NEUROSCI RES, V58, P88, DOI 10.1002/(SICI)1097-4547(19991001)58:1<88::AID-JNR9>3.0.CO