Journal Article

Dynamin, a membrane-remodelling GTPase

Ferguson, Shawn M., De Camilli, Pietro

2012

Overview

Key Points Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts. The mechanisms by which dynamin drives membrane fission have been the subject of intense debate. Recent crystallographic and cryo-electron microscopy studies of dynamin and DLPs support a model in which dynamin polymerization serves to bring two GTPase domains together, which allows GTP hydrolysis and the conformational changes in dynamin that are necessary for helix constriction and membrane fission. The role of dynamin is best defined during clathrin-dependent endocytosis and is essential only for a late step when membrane fission occurs. Gene-knockout studies in mice and the cells derived from them have provided numerous insights into dynamin function and the specific roles of the three dynamin isoforms. Dynamin 2 is ubiquitously expressed and has a housekeeping role in membrane dynamics. By contrast, dynamin 1 and dynamin 3 are specific to the nervous system and, although neither is essential for supporting a specific form of endocytosis at synapses, they may be important for allowing clathrin-mediated endocytosis to function over a very broad range of neuronal activities. Roles of abnormal dynamin function in genetic disease have begun to emerge. Whereas mutations in dynamin 2 show links to tissue-specific diseases, mutations in dynamin 1 specifically affect the nervous system. The dynamin GTPase mediates membrane remodelling during endocytosis. Through complementary approaches, including structural and genetic studies, the mechanisms by which dynamin regulates membrane fission events, and the unique physiological roles of its three isoforms, are becoming clear. Dynamin, the founding member of a family of dynamin-like proteins (DLPs) implicated in membrane remodelling, has a critical role in endocytic membrane fission events. The use of complementary approaches, including live-cell imaging, cell-free studies, X-ray crystallography and genetic studies in mice, has greatly advanced our understanding of the mechanisms by which dynamin acts, its essential roles in cell physiology and the specific function of different dynamin isoforms. In addition, several connections between dynamin and human disease have also emerged, highlighting specific contributions of this GTPase to the physiology of different tissues.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/80/313/1461 / 631/80/313/2377 / 692/699 / Animals / Biochemistry / Biology / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell Membrane - metabolism / Cell Membrane - physiology / Cells / Crystallography / Developmental Biology / Dynamins - chemistry / Dynamins - genetics / Dynamins - metabolism / Dynamins - physiology / Endocytosis - genetics / Endocytosis - physiology / GTP Phosphohydrolases - chemistry / GTP Phosphohydrolases - genetics / GTP Phosphohydrolases - metabolism / GTP Phosphohydrolases - physiology / Guanosine triphosphatase / Humans / Isoenzymes - chemistry / Isoenzymes - genetics / Isoenzymes - metabolism / Isoenzymes - physiology / Life Sciences / Mammals - genetics / Mammals - metabolism / Medicine / Membrane Fluidity - genetics / Membrane proteins / Membranes / Mice / Mitochondria / Models, Biological / Models, Molecular / Physiological aspects / Physiology / Plasma / Protein Conformation / Proteins / review-article / Roles / Stem Cells