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. Recent studies have shown that dynamin alone can catalyze fission of membrane tubules and vesicle formation from planar lipid templates, albeit inefficiently. We have recently proposed a two-stage model for dynamin-catalyzed fission (1). In stage one, mechanochemical activities of assembled dynamin helices induce localized curvature stress. In stage two the tightly packed lipid-interacting pleckstrin homology domains create a catalytic center that guides lipid remodeling through hemi-fission intermediates to drive membrane fission. Guided by recent X-ray crystallographic (2,3,4) and cryo-EM (4) structural studies of dynamin, we have been using site-directed fluorescent labeling of dynamin to the study nucleotide-dependent conformational changes required for dynamin-catalyzed fission. We have also identified dynamin partners that function synergistically with dynamin to catalyze membrane fission from SUPER templates. Together these studies shed new light on the mechanisms underlying dynamin-catalyzed membrane fission.1) Frolov and Schmid, Ann. Rev. Cell and Dev. Biol. 2011. PMID: 215994932) Ford, M.G.L.J., S. Jenni and J. Nunnari. 2011. Nature doi. 10.1038/nature10411.3) Faelber, K., Y.Posor, S. Gao, M. Held, Y. Roske, D. Schultz, V. Haucke, F. Noe, O. Daumke. 2011. Naure doi: 10.1038/nature10369.4) Chappie, J.S., J.A. Mears, S. Fung, M. Leonard, S.L. Schmid, R.A. Milligan, J.E. Hinshaw and F. Dyda. 2011. Cell 147:209-222.