Content area
Abstract
The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin bundles actin while forming a helical structure. At its full capacity, each dynamin helix captures 12–16 actin filaments on the outer rim of the helix. GTP hydrolysis by dynamin triggers disassembly of fully assembled dynamin helices, releasing free dynamin dimers/tetramers and facilitating Arp2/3-mediated branched actin polymerization. The assembly/disassembly cycles of dynamin promote continuous actin bundling to generate mechanically stiff actin super-bundles. Super-resolution and immunogold platinum replica electron microscopy revealed dynamin along actin bundles at the fusogenic synapse. These findings implicate dynamin as a unique multifilament actin-bundling protein that regulates the dynamics and mechanical strength of the actin cytoskeletal network.
Zhang et al. show that dynamin forms a helical structure with actin and, upon disruption, enhances branched actin polymerization, constituting a dynamic cycle to regulate actin cytoskeleton mechanical strength.
Details
; Lee, Donghoon M 1
; Jimah, John R 2 ; Gerassimov Nathalie 3 ; Yang Changsong 4 ; Kim, Sangjoon 3 ; Delgermaa, Luvsanjav 3 ; Winkelman, Jonathan 5 ; Mettlen Marcel 6 ; Abrams, Michael E 7 ; Kalia Raghav 8
; Keene, Peter 1
; Pandey Pratima 1 ; Ravaux Benjamin 1 ; Kim, Ji Hoon 3 ; Ditlev, Jonathon A 9
; Zhang, Guofeng 10 ; Rosen, Michael K 9
; Frost, Adam 11
; Alto, Neal M 7
; Gardel, Margaret 5 ; Schmid, Sandra L 6
; Svitkina, Tatyana M 4
; Hinshaw, Jenny E 2 ; Chen, Elizabeth H 12
1 UT Southwestern Medical Center, Department of Molecular Biology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
2 NIH, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165)
3 Johns Hopkins University School of Medicine, Department of Molecular Biology and Genetics, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311)
4 University of Pennsylvania, Department of Biology, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972)
5 University of Chicago, Department of Physics and Institute for Biophysical Dynamics, Chicago, USA (GRID:grid.170205.1) (ISNI:0000 0004 1936 7822)
6 UT Southwestern Medical Center, Department of Cell Biology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
7 UT Southwestern Medical Center, Department of Microbiology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
8 University of California, San Francisco, Department of Physiology, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811)
9 UT Southwestern Medical Center, Department of Biophysics and Howard Hughes Medical Institute, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
10 National Institute of Biomedical Imaging and Bioengineering, Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, Bethesda, USA (GRID:grid.280347.a) (ISNI:0000 0004 0533 5934)
11 University of California, San Francisco, Department of Biochemistry and Biophysics, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811)
12 UT Southwestern Medical Center, Department of Molecular Biology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121); Johns Hopkins University School of Medicine, Department of Molecular Biology and Genetics, Baltimore, USA (GRID:grid.21107.35) (ISNI:0000 0001 2171 9311); UT Southwestern Medical Center, Department of Cell Biology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)