title: GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase.
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.
authors.affiliation: Department of Neuroscience, School of Medicine, Johns Hopkins University, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: H R
authors.initials: HR
authors.lastname: Luo
authors.forename: A
authors.initials: A
authors.lastname: Saiardi
authors.forename: E
authors.initials: E
authors.lastname: Nagata
authors.forename: K
authors.initials: K
authors.lastname: Ye
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: T S
authors.initials: TS
authors.lastname: Jung
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: S
authors.initials: S
authors.lastname: Jain
authors.forename: A
authors.initials: A
authors.lastname: Sawa
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002417:Cattle; D019439:Chromaffin Cells / Q000166:cytology / Q000502:physiology; D003001:Cloning, Molecular; D004298:Dopamine / Q000378:metabolism; D005089:Exocytosis; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D016716:PC12 Cells; D010710:Phosphates / Q000378:metabolism; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000502:physiology*; D014162:Transfection; D020826:rab3A GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D018722:Nicotinic Agonists; D010710:Phosphates; C434523:Rab3il1 protein, rat; C092115:Rab3ip protein, rat; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D020932:Nerve Growth Factor; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase; D020826:rab3A GTP-Binding Protein; D004298:Dopamine