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

Ruihui Zhang, Donghoon M. Lee, John R. Jimah, Nathalie Gerassimov, Changsong Yang, Sangjoon Kim, Delgermaa Luvsanjav, Jonathan Winkelman, Marcel Mettlen, Michael E. Abrams, Raghav Kalia, Peter Keene, Pratima Pandey, Benjamin Ravaux, Ji Hoon Kim, Jonathon A. Ditlev, Guofeng Zhang, Michael K. Rosen, Adam Frost, Neal M. AltoMargaret Gardel, Sandra L. Schmid, Tatyana M. Svitkina, Jenny E. Hinshaw, Elizabeth H. Chen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)674-688
Number of pages15
JournalNature cell biology
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Zhang, R., Lee, D. M., Jimah, J. R., Gerassimov, N., Yang, C., Kim, S., Luvsanjav, D., Winkelman, J., Mettlen, M., Abrams, M. E., Kalia, R., Keene, P., Pandey, P., Ravaux, B., Kim, J. H., Ditlev, J. A., Zhang, G., Rosen, M. K., Frost, A., ... Chen, E. H. (2020). Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein. Nature cell biology, 22(6), 674-688. https://doi.org/10.1038/s41556-020-0519-7