@article{79c719377c4347839bee42a684cca108,
title = "Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein",
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.",
author = "Ruihui Zhang and Lee, {Donghoon M.} and Jimah, {John R.} and Nathalie Gerassimov and Changsong Yang and Sangjoon Kim and Delgermaa Luvsanjav and Jonathan Winkelman and Marcel Mettlen and Abrams, {Michael E.} and Raghav Kalia and Peter Keene and Pratima Pandey and Benjamin Ravaux and Kim, {Ji Hoon} and Ditlev, {Jonathon A.} and Guofeng Zhang and Rosen, {Michael K.} and Adam Frost and Alto, {Neal M.} and Margaret Gardel and Schmid, {Sandra L.} and Svitkina, {Tatyana M.} and Hinshaw, {Jenny E.} and Chen, {Elizabeth H.}",
note = "Funding Information: We thank the Bloomington Drosophila Stock Center for the fly stocks, B. Paterson for the myosin heavy chain antibody, K. Reed and A. Mohanakrishnan for help with protein purification and GTPase activity measurement, M. Mikolaj for help with generating the model in IMOD, H. He and H. Wang for help with generating the cryo-tomograms using SerialEM, K. Chinthalapudi for providing the actin filament for modelling in Chimera, and the Cryo-Electron Microscopy Core, NIDDK, NIH for Cryo-ET analyses. This work was supported by: NIH grants (R01 AR053173 and R01 GM098816), an American Heart Association Established Investigator Award and a HHMI Faculty Scholar Award to E.H.C.; an NIH grant (R01 GM095977) to T.M.S.; an NIH grant (R01 GM42455) and Welch Foundation grant (I-1823) to S.L.S.; an NIH grant (R01 GM104032) to M.G.; an NIH grant (R01 AI083359), HHMI and Simons Foundation grant and Welch Foundation grant (I-1704) to N.M.A.; and an NIH grant (R01 GM127673), Chan Zuckerberg Biohub Investigator Award and HHMI Faculty Scholar Award to A.F. M.K.R. is an HHMI investigator. R.Z. was supported by an American Heart Association postdoctoral fellowship. D.M.L. was supported by a Canadian Institute of Health Research postdoctoral fellowship. N.G. was supported by an American Heart Association predoctoral fellowship. J.A.D. was supported by a National Research Service Award from NIDDK (F32 DK101188). The electron microscopy imaging experiments at UT Southwestern were supported in part by an NIH grant (1S10OD021685-01A1). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = jun,
day = "1",
doi = "10.1038/s41556-020-0519-7",
language = "English (US)",
volume = "22",
pages = "674--688",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "6",
}