Dynamin GTPase regulated by protein kinase C phosphorylation in nerve terminals.
Dynamin is a microtubule-binding protein with a microtubule-activated GTPase activity. The gene encoding dynamin is mutated in shibire, a Drosophila mutant defective in endocytosis in nerve terminals and other cells. These observations place dynamin into two distinct functional contexts, suggesting roles in microtubule-based motility or in endocytosis. We report here that dynamin is identical to the neuronal phosphoprotein dephosphin (P96), originally identified by its stimulus-dependent dephosphorylation in nerve terminals. Dynamin is a protein doublet of M(r) 94 and 96K arising by alternative splicing of its primary transcript. In the nerve terminal, both forms of dynamin are phosphorylated by protein kinase C (PKC) and are quantitatively dephosphorylated on excitation. In vitro, dynamin is also phosphorylated by casein kinase II which inhibits PKC phosphorylation. Phosphorylation by PKC but not by casein kinase II enhances the GTPase activity of dynamin 12-fold. The dynamins are therefore a group of nerve terminal phosphoproteins whose GTPase is regulated by phosphorylation in parallel with synaptic vesicle recycling. The regulation of dynamin GTPase could serve as the trigger for the rapid endocytosis of synaptic vesicles after exocytosis.
Robinson
P J
PJ
Endocrine Unit, John Hunter Hospital, Newcastle, New South Wales, Australia.
Sontag
J M
JM
Liu
J P
JP
Fykse
E M
EM
Slaughter
C
C
McMahon
H
H
Südhof
T C
TC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013570:Synaptic Membranes / Q000378:metabolism
D029721:Drosophila Proteins; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases; D034281:Dynamins; C439628:shi protein, Drosophila