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

TitleDynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhang, R, Lee, DM, Jimah, JR, Gerassimov, N, Yang, C, Kim, S, Luvsanjav, D, Winkelman, J, Mettlen, M, Abrams, ME, Kalia, R, Keene, P, Pandey, P, Ravaux, B, Kim, JHoon, Ditlev, JA, Zhang, G, Rosen, MK, Frost, A, Alto, NM, Gardel, M, Schmid, SL, Svitkina, TM, Hinshaw, JE, Chen, EH
JournalNat Cell Biol
Volume22
Issue6
Pagination674-688
Date Published2020/06/30
ISSN1476-4679
KeywordsActin Cytoskeleton, Actin-Related Protein 2-3 Complex, Actins, Amino Acid Sequence, Animals, Cell Communication, Drosophila melanogaster, Dynamins, Endocytosis, Female, Guanosine Triphosphate, Male, Myoblasts, Protein Binding, Sequence Homology
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.

DOI10.1038/s41556-020-0519-7
Alternate JournalNat Cell Biol
PubMed ID32451441
PubMed Central IDPMC7953826
Grant ListR01 GM104032 / GM / NIGMS NIH HHS / United States
F32 DK101188 / DK / NIDDK NIH HHS / United States
S10 OD021685 / OD / NIH HHS / United States
Z01 DK060100 / ImNIH / Intramural NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
/ / CIHR / Canada
R35 GM136316 / GM / NIGMS NIH HHS / United States
R01 AR053173 / AR / NIAMS NIH HHS / United States
R01 GM042455 / GM / NIGMS NIH HHS / United States
R01 GM098816 / GM / NIGMS NIH HHS / United States
R01 GM095977 / GM / NIGMS NIH HHS / United States
R01 AI083359 / AI / NIAID NIH HHS / United States
R01 GM127673 / GM / NIGMS NIH HHS / United States