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., Alto, N.M., Gardel, M., Schmid, S.L., Svitkina, T.M., Hinshaw, J.E., Chen, E.H. (2020). Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein.  Nat. Cell Biol. 22(6): 674--688.

FBrf0246723

Research paper

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.

PMC7953826 (PMC) (EuropePMC)