Mechanism of Dynamin‐Catalyzed Membrane Fission

Abstract

Dynamin, best studied for its role in clathrin‐mediated endocytosis, is the prototypical member of a family of multi‐domain GTPases involved in fission and remodeling of multiple organelles. Dynamin alone can catalyze fission of membrane tubules and vesicle formation from planar lipid templates. We recently proposed a two‐stage model for dynamin‐catalyzed fission (Frolov and Schmid, Ann. Rev. Cell and Dev. Biol. 2011. 27: 79). In stage one, mechanochemical activities of assembled dynamin helices induce localized curvature stress. In stage two the tightly packed lipid‐interacting pleckstrin homology domains insert hydrophobic wedges into the bilayer to create a catalytic center that guides lipid remodeling and drives membrane fission through hemi‐fission intermediates. We have been using site‐directed fluorescent labeling of dynamin to the study nucleotide‐dependent conformational changes required for dynamin‐catalyzed fission. Our data suggests that a concerted conformational change and coordinated GTP hydrolysis are required for dynamin‐catalyzed fission. We are also studying the role of BAR domain‐containing proteins as dynamin partners in membrane fission.