Regulation of dynamin I GTPase activity by G protein βγ subunits and phosphatidylinositol 4,5-bisphosphate

Dynamin I is a 100-kDa GTPase that plays an important role in the recycling of synaptic vesicles. Hydrolysis of GTP by dynamin is thought to be a critical step in fission of coated pits to form coated vesicles. We report that the heterotrimeric G protein βγ subunit complex (G(βγ)) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P₂) are negative and positive regulators of dynamin GTPase activity, respectively. Furthermore, the apparent affinity of dynamin for G(βγ) is substantially enhanced by PtdIns(4,5)P₂. However, the GTPase activity of oligomeric dynamin is unaffected by G(βγ). The effects of heterotrimeric G proteins on endocytosis may thus be mediated directly and not involve more remote aspects of their signaling properties.