Dissecting dynamin's role in clathrin-mediated endocytosis

The GTPase dynamin is essential for clathrin-mediated endocytosis (CME), but its exact function and mechanism of action has been controversial. Here we review findings that have led to current models for dynamin function, either as a mechanochemical enzyme driving membrane fission or as a regulatory GTPase monitoring rate limiting steps in CME. However, these models are not mutually exclusive and subsequent studies have provided evidence for both dynamin functions. Here we present recent evidence derived from divergent in vivo and in vitro approaches that dynamin plays a dual role in CME, functioning at early stages as a fidelity monitor to regulate clathrin-coated pit maturation and at later stages to directly catalyze membrane fission and clathrin-coated vesicle formation.