The mechanisms of dynamin-actin interaction

Ruihui Zhang, Nathalie Gerassimov, Donghoon M. Lee, John R. Jimah, 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. Alto, Margaret GardelSandra L. Schmid, Jenny E. Hinshaw, Elizabeth H. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-cell fusion is an indispensable process in the conception, development and physiology of multicellular organisms. Here we demonstrate a direct and noncanonical role for dynamin, best known as a fission GTPase in endocytosis, in cell-cell fusion. Our genetic and cell biological analyses show that dynamin colocalizes within the F-actin-enriched podosome-like structures at the fusogenic synapse, which is required for generating invasive membrane protrusions and myoblast fusion in vivo, in an endocytosis-independent manner. Biochemical, negative stain EM and cryo-electron tomography (cryo-ET) analyses revealed that dynamin forms helices that directly bundles actin filaments by capturing multiple actin filaments at their outer rim via interactions with dynamin’s proline-rich domain. GTP hydrolysis by dynamin triggers disassembly of the dynamin helix, exposes the sides of the actin filaments, promotes dynamic Arp2/3-mediated branched actin polymerization, and generates a mechanically stiff actin network. Thus, dynamin functions as a unique actin-bundling protein that enhances mechanical force generation by the F-actin network in a GTPase-dependent manner. Our findings have universal implications for understanding dynamin-actin interactions in various cellular processes beyond cell-cell fusion.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Mar 25 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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