1. Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein
- Author
-
Zhang, Ruihui, Lee, Donghoon M, Jimah, John R, Gerassimov, Nathalie, Yang, Changsong, Kim, Sangjoon, Luvsanjav, Delgermaa, Winkelman, Jonathan, Mettlen, Marcel, Abrams, Michael E, Kalia, Raghav, Keene, Peter, Pandey, Pratima, Ravaux, Benjamin, Kim, Ji Hoon, Ditlev, Jonathon A, Zhang, Guofeng, Rosen, Michael K, Frost, Adam, Alto, Neal M, Gardel, Margaret, Schmid, Sandra L, Svitkina, Tatyana M, Hinshaw, Jenny E, and Chen, Elizabeth H
- Subjects
Underpinning research ,1.1 Normal biological development and functioning ,Actin 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 ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - 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.
- Published
- 2020