title: Calcium binds dynamin I and inhibits its GTPase activity.
abstract: Synaptic vesicle recycling is a neuronal specialization of endocytosis that requires the GTPase activity of dynamin I and is triggered by membrane depolarization and Ca2+ entry. To establish the relationship between dynamin I GTPase activity and Ca2+, we used purified dynamin I and analyzed its interaction with Ca2+ in vitro. We report that Ca2+ bound to dynamin I and this was abolished by deletion of dynamin's C-terminal tail. Phosphorylation of dynamin I by protein kinase C promoted formation of a dynamin I tetramer and increased Ca2+ binding to the protein. Moreover, Ca2+ inhibited dynamin I GTPase activity after stimulation by phosphorylation or by phospholipids but not after stimulation with a GST-SH3 fusion protein containing the SH3 domain of phosphoinositide 3-kinase. These results suggest that in resting nerve terminals, phosphorylation of dynamin I by protein kinase C converts it to a tetramer that functions as a Ca(2+)-sensing protein. By binding to Ca2+, dynamin I GTPase activity is specifically decreased, possibly to regulate synaptic vesicle recycling.
authors.affiliation: Endocrine Unit, John Hunter Hospital, Newcastle, New South Wales, Australia.
authors.forename: J P
authors.initials: JP
authors.lastname: Liu
authors.forename: Q X
authors.initials: QX
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Baldwin
authors.forename: P J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000502:physiology*; D034284:Dynamin I; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D010447:Peptide Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015345:Oligonucleotide Probes; D011493:Protein Kinase C; D010447:Peptide Hydrolases; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium