The role of the PH domain and SH3 binding domains in dynamin function.
Dynamin, a 100 kD GTPase, is necessary for the normal development and function of mammalian neural tissue. In neurons, it is necessary for the biogenesis of synaptic vesicles, and in other cell types dynamin has a general and important role in clathrin mediated receptor endocytosis. Different isoforms function as molecular scissors either during the formation of coated vesicles from plasma membrane coated pits, or during the release of intracellular vesicles from donor membranes. The mechanism entails the formation of a horseshoe-shaped dynamin polymer at the neck of the budding vesicle, followed by neck scission through a GTP hydrolysis dependent activity. The primary sequence of dynamin contains several C-terminal SH3 binding proline motifs, a central pleckstrin homology (PH) domain, and an N-terminal GTPase domain. Each of these domains appears to play a distinct role in dynamin function. Dynamin is activated by stimulus coupled PKC phosphorylation in brain, possibly mediated through PKC interactions with the PH domain. Further, SH3 domain interactions with the C-terminal sequences and phophatidylinositol/G beta gamma interactions with the PH domain also increase dynamin GTPase activity. Each of these various regulatory mechanisms is important in dynamin function during vesicle budding, although the means by which these mechanisms integrate in the overall function of dynamin remains to be elucidated.
Scaife
R M
RM
Institut de Biologie Structurale Jean-Pierre Ebel (CEA-CNRS), Grenoble, France.
Margolis
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains / Q000502:physiology*
D001798:Blood Proteins; D010750:Phosphoproteins; C039077:platelet protein P47; D020558:GTP Phosphohydrolases; D034281:Dynamins