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

Yaping Tu, Surendra K. Nayak, Jimmy Woodson, Elliott M. Ross

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)52273-52281
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number52
DOIs
StatePublished - Dec 26 2003

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RGS Proteins
Synapsins
GTPase-Activating Proteins
Phosphorylation
Brain
Inhibition (Psychology)
p21-Activated Kinases
Chromaffin Cells
Synaptic Vesicles
Platelets
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Serine
Neurons
Machinery
Actin Cytoskeleton
Actins
Protein Isoforms
Blood Platelets

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphorylation-regulated Inhibition of the Gz GTPase-activating Protein Activity of RGS Proteins by Synapsin I. / Tu, Yaping; Nayak, Surendra K.; Woodson, Jimmy; Ross, Elliott M.

In: Journal of Biological Chemistry, Vol. 278, No. 52, 26.12.2003, p. 52273-52281.

Research output: Contribution to journalArticle

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