ACTIVATION OF DYNAMIN GTPASE BY ACIDIC PHOSPHOLIPIDS AND ENDOGENOUS RAT-BRAIN VESICLES

Dynamin is a GTPase thought to play a role in endocytosis based on gen etic analysis of its homolog in Drosophila melanogaster shibire. Previ ous studies have stressed an in vitro association with microtubules, t hough additional evidence suggests that dynamin associates with membra nous organelles. In an analysis of the enzymatic and membrane binding properties of dynamin, we have found that the acidic phospholipids, ph osphatidylserine, phosphatidylglycerol, and phosphatidylinositol, are able to stimulate GTP hydrolysis in a manner similar to activation pre viously shown with microtubules. A neutral phospholipid, phosphatidylc holine, had no effect on dynamin GTPase. Activation of dynamin was bip hasic, with a decrease in activity back to basal levels with increased concentrations of either microtubules or liposomes. A comparison betw een GTPase stimulation induced by microtubules and that by phospholipi ds suggests that ionic interactions between the basic C-terminal domai n of dynamin and the negatively charged microtubule or phospholipid he ad group are important. In support of this, GTPase stimulation by thes e agents in combination was not additive. A salt-extracted membrane fr action from brain tissue also activated dynamin GTPase, though to a lo wer extent than pure phospholipids. These results suggest that membran e components could be responsible for some aspects of the regulation o f dynamin function in vivo.