Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein.

Autor: Zhang R; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA., Lee DM; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA., Jimah JR; Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA., Gerassimov N; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Yang C; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Kim S; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Luvsanjav D; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Winkelman J; Department of Physics and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA., Mettlen M; Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA., Abrams ME; Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA., Kalia R; Department of Physiology, University of California, San Francisco, San Francisco, CA, USA., Keene P; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA., Pandey P; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA., Ravaux B; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA., Kim JH; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Ditlev JA; Department of Biophysics and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA., Zhang G; Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD, USA., Rosen MK; Department of Biophysics and Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA., Frost A; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA., Alto NM; Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA., Gardel M; Department of Physics and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA., Schmid SL; Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA., Svitkina TM; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Hinshaw JE; Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA., Chen EH; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA. elizabeth.chen@utsouthwestern.edu.; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. elizabeth.chen@utsouthwestern.edu.; Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA. elizabeth.chen@utsouthwestern.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2020 Jun; Vol. 22 (6), pp. 674-688. Date of Electronic Publication: 2020 May 25.
DOI: 10.1038/s41556-020-0519-7
Abstrakt: 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.
Databáze: MEDLINE