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Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin

The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin bar...

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Autores principales: Mizuno, Hiroaki, Tanaka, Kotaro, Yamashiro, Sawako, Narita, Akihiro, Watanabe, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984536/
https://www.ncbi.nlm.nih.gov/pubmed/29760064
http://dx.doi.org/10.1073/pnas.1803415115
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author Mizuno, Hiroaki
Tanaka, Kotaro
Yamashiro, Sawako
Narita, Akihiro
Watanabe, Naoki
author_facet Mizuno, Hiroaki
Tanaka, Kotaro
Yamashiro, Sawako
Narita, Akihiro
Watanabe, Naoki
author_sort Mizuno, Hiroaki
collection PubMed
description The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin barely associates. In vitro, F-actin decorated with cofilin exhibits a marked increase in the filament twist. On the other hand, a mammalian formin mDia1 rotates along the long-pitch actin helix during processive actin elongation (helical rotation). Helical rotation may impose torsional force on F-actin in the opposite direction of the cofilin-induced twisting. Here, we show that helical rotation of mDia1 converts F-actin resistant to cofilin both in vivo and in vitro. F-actin assembled by mDia1 without rotational freedom became more resistant to the severing and binding activities of cofilin than freely rotatable F-actin. Electron micrographic analysis revealed untwisting of the long-pitch helix of F-actin elongating from mDia1 on tethering of both mDia1 and the pointed end side of the filament. In cells, single molecules of mDia1ΔC63, an activated mutant containing N-terminal regulatory domains, showed tethering to cell structures more frequently than autoinhibited wild-type mDia1 and mDia1 devoid of N-terminal domains. Overexpression of mDia1ΔC63 induced the formation of F-actin, which has prolonged lifetime and accelerates dissociation of cofilin. Helical rotation of formins may thus serve as an F-actin stabilizing mechanism by which a barbed end-bound molecule can enhance the stability of a filament over a long range.
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spelling pubmed-59845362018-06-07 Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin Mizuno, Hiroaki Tanaka, Kotaro Yamashiro, Sawako Narita, Akihiro Watanabe, Naoki Proc Natl Acad Sci U S A PNAS Plus The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin barely associates. In vitro, F-actin decorated with cofilin exhibits a marked increase in the filament twist. On the other hand, a mammalian formin mDia1 rotates along the long-pitch actin helix during processive actin elongation (helical rotation). Helical rotation may impose torsional force on F-actin in the opposite direction of the cofilin-induced twisting. Here, we show that helical rotation of mDia1 converts F-actin resistant to cofilin both in vivo and in vitro. F-actin assembled by mDia1 without rotational freedom became more resistant to the severing and binding activities of cofilin than freely rotatable F-actin. Electron micrographic analysis revealed untwisting of the long-pitch helix of F-actin elongating from mDia1 on tethering of both mDia1 and the pointed end side of the filament. In cells, single molecules of mDia1ΔC63, an activated mutant containing N-terminal regulatory domains, showed tethering to cell structures more frequently than autoinhibited wild-type mDia1 and mDia1 devoid of N-terminal domains. Overexpression of mDia1ΔC63 induced the formation of F-actin, which has prolonged lifetime and accelerates dissociation of cofilin. Helical rotation of formins may thus serve as an F-actin stabilizing mechanism by which a barbed end-bound molecule can enhance the stability of a filament over a long range. National Academy of Sciences 2018-05-29 2018-05-14 /pmc/articles/PMC5984536/ /pubmed/29760064 http://dx.doi.org/10.1073/pnas.1803415115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Mizuno, Hiroaki
Tanaka, Kotaro
Yamashiro, Sawako
Narita, Akihiro
Watanabe, Naoki
Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title_full Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title_fullStr Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title_full_unstemmed Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title_short Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin
title_sort helical rotation of the diaphanous-related formin mdia1 generates actin filaments resistant to cofilin
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984536/
https://www.ncbi.nlm.nih.gov/pubmed/29760064
http://dx.doi.org/10.1073/pnas.1803415115
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