The many implications of actin filament helicity

Jégou, Antoine; Romet-Lemonne, Guillaume

doi:10.1016/j.semcdb.2019.10.018

Cited by 37 publications

(28 citation statements)

References 116 publications

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“…Our results illustrate how factors of different natures can come together to regulate actin assembly (Jégou and Romet-Lemonne, 2016). The interplay between ABPs and mechanical factors, in particular, is currently under intense scrutiny (Harris et al, 2018;Jegou and Romet-Lemonne, 2019;Schramm et al, 2017;Suzuki et al, 2020;Wioland et al, 2019b;Zimmermann and Kovar, 2019). Today, PTMs of actin are emerging as a key regulatory factor of actin assembly (Varland et al, 2019) and how they modify interactions with ABPs is mostly unknown.…”

Section: Discussionmentioning

confidence: 82%

Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly

Wioland

Frémont

Guichard

et al. 2020

Preprint

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Proteins of the ADF/cofilin family play a central role in the disassembly of actin filaments, and their activity must be tightly regulated in cells. Recently, the oxidation of actin filaments by the enzyme MICAL1 was found to amplify the severing action of cofilin through unclear mechanisms. Two essential factors normally prevent filament disassembly: the inactivation of cofilin by phosphorylation, and the protection of filaments by tropomyosins, but whether actin oxidation might interfere with these safeguard mechanisms is unknown. Using single filament experiments in vitro, we found that actin filament oxidation by MICAL1 increases, by several orders of magnitude, both cofilin binding and severing rates, explaining the dramatic synergy between oxidation and cofilin for filament disassembly. Remarkably, we found that actin oxidation bypasses the need for cofilin activation by dephosphorylation. Indeed, non-activated, phosphomimetic S3D-cofilin binds and severs oxidized actin filaments rapidly, in conditions where non-oxidized filaments are unaffected. Finally, tropomyosin Tpm1.8 loses its ability to protect filaments from cofilin severing activity when actin is oxidized by MICAL1. Together, our results show that MICAL1-induced oxidation of actin filaments suppresses their physiological protection from the action of cofilin. We propose that in cells, direct post-translational modification of actin filaments by oxidation is a way to trigger their severing, in spite of being decorated by tropomyosin, and without requiring the activation of cofilin.

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Section: Discussionmentioning

confidence: 82%

Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly

Wioland

Frémont

Guichard

et al. 2020

Preprint

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“…In accordance with evidence that actin filaments exhibit intrinsic structural polymorphism in response to varying environmental conditions [31][32][33], structural transitions along F-actin induced by ABPs are believed to be important for cooperation with fragmentation due to myosin motor activity [28,34]. Thus, several studies suggest that binding of a range of ABPs allosterically produce long-range structural transitions along the actin filament [35][36][37][38][39][40][41][42][43][44].…”

Section: Introductionmentioning

confidence: 73%

Myosin and gelsolin cooperate in actin filament severing and actomyosin motor activity

Vemula

Huber

Ušaj

et al. 2021

Journal of Biological Chemistry

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Actin is a major intracellular protein with key functions in cellular motility, signaling, and structural rearrangements. Its dynamic behavior, such as polymerization and depolymerization of actin filaments in response to intracellular and extracellular cues, is regulated by an abundance of actin binding proteins. Out of these, gelsolin is one of the most potent for filament severing. However, myosin motor activity also fragments actin filaments through motor-induced forces, suggesting that these two proteins could cooperate to regulate filament dynamics and motility. To test this idea, we used an in vitro motility assay, where actin filaments are propelled by surface-adsorbed heavy meromyosin (HMM) motor fragments. This allows studies of both motility and filament dynamics using isolated proteins. Gelsolin, at both nanomolar and micromolar Ca 2+ concentration, appreciably enhanced actin filament severing caused by HMM-induced forces at 1 mM MgATP, an effect that was increased at higher HMM motor density. This finding is consistent with cooperativity between actin filament severing by myosin-induced forces and by gelsolin. We also observed reduced sliding velocity of the HMM-propelled filaments in the presence of gelsolin, providing further support of myosin-gelsolin cooperativity. Total internal reflection fluorescence microscopy–based single molecule studies corroborated that the velocity reduction was a direct effect of gelsolin binding to the filament and revealed different filament severing pattern of stationary and HMM propelled filaments. Overall, the results corroborate cooperative effects between gelsolin-induced alterations in the actin filaments and changes due to myosin motor activity leading to enhanced F-actin severing of possible physiological relevance.

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“…as proposed for cofilin [28,30]. In accordance with evidence that actin filaments exhibit intrinsic structural polymorphism in response to varying environmental conditions [31][32][33], structural transitions along F-actin induced by ABPs are believed to be important for cooperation with fragmentation due to myosin motor activity [29,34]. Thus, several studies suggest that binding of a range of ABPs allosterically produce long-range structural transitions along the actin filament [35][36][37][38][39][40][41][42][43][44].…”

Section: Introductionmentioning

confidence: 62%

Myosin-gelsolin cooperativity in actin filament severing and actomyosin motor activity

Vemula

Huber

Ušaj

et al. 2020

Preprint

View full text Add to dashboard Cite

Actin is a major intracellular protein with key functions in cellular motility, signalling and structural rearrangements. Its dynamic behavior with actin filaments (F-actin) polymerising and depolymerising in response to intracellular changes, is controlled by actin-binding proteins (ABPs). Gelsolin is one of the most potent filament severing ABPs. However, myosin motors that interact with actin in the presence of ATP also produce actin filament fragmentation through motor induced shearing forces. To test the idea that gelsolin and myosin cooperate in these processes we used the in vitro motility assay, where actin filaments are propelled by surface-adsorbed heavy meromyosin (HMM) motor fragments. This allows studies of both motility and filament dynamics using isolated proteins. Gelsolin (5 nM) at very low [Ca2+] (free [Ca2+] ∼6.8 nM) appreciably enhanced actin filament severing caused by HMM-induced forces at 1 mM [MgATP], an effect that was increased at increased HMM motor density. This finding is consistent with cooperativity between actin filament severing by myosin-induced forces and by gelsolin. As further support of myosin-gelsolin cooperativity we observed reduced sliding velocity of the HMM propelled filaments in the presence of gelsolin. Overall, the results corroborate ideas for cooperative effects between gelsolin-induced alterations in the actin filaments and changes due to myosin motor activity, leading among other effects to enhanced F-actin severing of possible physiological relevance.

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The many implications of actin filament helicity

Cited by 37 publications

References 116 publications

Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly

Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly

Myosin and gelsolin cooperate in actin filament severing and actomyosin motor activity

Myosin-gelsolin cooperativity in actin filament severing and actomyosin motor activity

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