Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein. Author Ruihui Zhang, Donghoon Lee, John Jimah, Nathalie Gerassimov, Changsong Yang, Sangjoon Kim, Delgermaa Luvsanjav, Jonathan Winkelman, Marcel Mettlen, Michael Abrams, Raghav Kalia, Peter Keene, Pratima Pandey, Benjamin Ravaux, Ji Kim, Jonathon Ditlev, Guofeng Zhang, Michael Rosen, Adam Frost, Neal Alto, Margaret Gardel, Sandra Schmid, Tatyana Svitkina, Jenny Hinshaw, Elizabeth Chen Publication Year 2020 Type Journal Article 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. Keywords Animals, Protein Binding, Amino Acid Sequence, Cell Communication, Female, Male, Drosophila melanogaster, Actins, Actin Cytoskeleton, Sequence Homology, Endocytosis, Guanosine Triphosphate, Myoblasts, Actin-Related Protein 2-3 Complex, Dynamins Journal Nat Cell Biol Volume 22 Issue 6 Pages 674-688 Date Published 2020 Jun ISSN Number 1476-4679 DOI 10.1038/s41556-020-0519-7 Alternate Journal Nat Cell Biol PMCID PMC7953826 PMID 32451441 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML