GRAB: A physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase

被引:81
作者
Luo, HR
Saiardi, A
Nagata, E
Ye, KQ
Yu, HB
Jung, TS
Luo, XJ
Jain, S
Sawa, A
Snyder, SH
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 & Behav Sci, Baltimore, MD 21205 USA
关键词
D O I
10.1016/S0896-6273(01)00384-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Diphosphoinositol-pentakisphosphate (InsP7) and bis-diphosphoinositol tetrakisphosphate (InsP8) possess pyrophosphate bonds. InsP7 is formed from inositol hexakisphosphate (InsP6) by recently identified InsP6 kinases designated InsP6K1 and InsP6K2. We now report the identification, cloning, and characterization of a novel protein, GRAB (guanine nucleotide exchange factor for Rab3A), which interacts with both InsP6K1 and Rab3A, a Ras-like GTPase that regulates synaptic vesicle exocytosis. GRAB is a physiologic GEF (guanine nucleotide exchange factor) for Rab3A. Consistent with a role of Rab3A in synaptic vesicle exocytosis, GRAB regulates depolarization-induced release of dopamine from PC12 cells and nicotinic agonist-induced hGH release from bovine adrenal chromaffin cells. The association of InsP6K1 with GRAB fits with a role for InsP7 in vesicle exocytosis.
引用
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页码:439 / 451
页数:13
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