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J. Biol. Chem. 278 (52): 52273-52281

© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphorylation-regulated Inhibition of the Gz GTPase-activating Protein Activity of RGS Proteins by Synapsin I*

Yaping Tu{ddagger}, Surendra K. Nayak§, Jimmy Woodson, , and Elliott M. Ross¶

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041

Abstract: Synapsins are neuronal proteins that bind and cluster synaptic vesicles in the presynaptic space, presumably by anchoring to actin filaments, but specific regulatory functions of the synapsins are unknown. We found that a sub-population of brain synapsin Ia, a splice variant of one of three synapsin isoforms, inhibits the GTPase-activating protein (GAP) activity of several RGS proteins. Inhibition is highly selective for Gαz, a member of the Gi family that is found in neurons, platelets, adrenal chromaffin cells, and a few other neurosecretory cells. Gz has been indirectly implicated in the regulation of secretion. Synapsin Ia constitutes a major fraction of the total GAP-inhibitory activity in brain, and its inhibitory activity is absent from the brains of synapsin I-/-/II-/- mice. Inhibition depends on the cationic D/E domain of synapsin. Phosphorylation of synapsin Ia at serine 9 by either cyclic AMP-dependent protein kinase or p21-activated protein kinase (PAK1) attenuates its potency as a GAP inhibitor more than 7-fold. Synapsin can thus act as a phosphorylation-modulated mediator of feedback regulation of Gz signaling by the synaptic machinery.


Received for publication August 29, 2003. Revision received October 9, 2003.

To whom correspondence should be addressed: Dept. of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9041. Tel.: 214-648-8717; Fax: 214-648-2994; E-mail: ross{at}utsw.swmed.edu.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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