TY - JOUR
T1 - Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
AU - Grintsevich, Elena E.
AU - Ahmed, Giasuddin
AU - Ginosyan, Anush A.
AU - Wu, Heng
AU - Rich, Shannon K.
AU - Reisler, Emil
AU - Terman, Jonathan R.
N1 - Funding Information:
We thank colleagues and members of the Reisler and Terman labs for comments and assistance on the manuscript. We also thank H. Aberle, L. Cooley, H. Higgs, D. Kovar, H. Kramer, B. Lee, J. Merriam, M. Quinlan, and the Bloomington Drosophila Stock Center for reagents and/or assistance. The work was supported by an NIH grant GM077190 to E.R. and NIH (MH085923) and Welch Foundation (I-1749) grants to J.R.T.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Cellular events require the spatiotemporal interplay between actin assembly and actin disassembly. Yet, how different factors promote the integration of these two opposing processes is unclear. In particular, cellular monomeric (G)-actin is complexed with profilin, which inhibits spontaneous actin nucleation but fuels actin filament (F-actin) assembly by elongation-promoting factors (formins, Ena/VASP). In contrast, site-specific F-actin oxidation by Mical promotes F-actin disassembly and release of polymerization-impaired Mical-oxidized (Mox)-G-actin. Here we find that these two opposing processes connect with one another to orchestrate actin/cellular remodeling. Specifically, we find that profilin binds Mox-G-actin, yet these complexes do not fuel elongation factors’-mediated F-actin assembly, but instead inhibit polymerization and promote further Mox-F-actin disassembly. Using Drosophila as a model system, we show that similar profilin–Mical connections occur in vivo – where they underlie F-actin/cellular remodeling that accompanies Semaphorin–Plexin cellular/axon repulsion. Thus, profilin and Mical combine to impair F-actin assembly and promote F-actin disassembly, while concomitantly facilitating cellular remodeling and plasticity.
AB - Cellular events require the spatiotemporal interplay between actin assembly and actin disassembly. Yet, how different factors promote the integration of these two opposing processes is unclear. In particular, cellular monomeric (G)-actin is complexed with profilin, which inhibits spontaneous actin nucleation but fuels actin filament (F-actin) assembly by elongation-promoting factors (formins, Ena/VASP). In contrast, site-specific F-actin oxidation by Mical promotes F-actin disassembly and release of polymerization-impaired Mical-oxidized (Mox)-G-actin. Here we find that these two opposing processes connect with one another to orchestrate actin/cellular remodeling. Specifically, we find that profilin binds Mox-G-actin, yet these complexes do not fuel elongation factors’-mediated F-actin assembly, but instead inhibit polymerization and promote further Mox-F-actin disassembly. Using Drosophila as a model system, we show that similar profilin–Mical connections occur in vivo – where they underlie F-actin/cellular remodeling that accompanies Semaphorin–Plexin cellular/axon repulsion. Thus, profilin and Mical combine to impair F-actin assembly and promote F-actin disassembly, while concomitantly facilitating cellular remodeling and plasticity.
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U2 - 10.1038/s41467-021-25781-3
DO - 10.1038/s41467-021-25781-3
M3 - Article
C2 - 34545088
AN - SCOPUS:85115390146
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5542
ER -