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

Hongbo R. Luo, Adolfo Saiardi, Eiichiro Nagata, Keqiang Ye, Hongbo Yu, Thomas S. Jung, Xiaojiang Luo, Sima Jain, Akira Sawa, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)439-451
Number of pages13
JournalNeuron
Volume31
Issue number3
DOIs
StatePublished - Aug 16 2001

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ASJC Scopus subject areas

  • Neuroscience(all)

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