Assembly and Turnover of Short Actin Filaments by the Formin INF2 and Profilin

Gurel, Pinar S.; A, Mu; Guo, Bingquian; Shu, Rui; Mierke, Dale F.; Higgs, Henry N.

doi:10.1074/jbc.m115.670166

Cited by 32 publications

(34 citation statements)

References 48 publications

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“…Our stochastic model for CaAR shows that the extent and speed of actin reorganization at the cortex and ER can only be achieved if Ca 2+ simultaneously increases the rate of nucleation at the ER and the overall rate of actin depolymerization. Interestingly, the key regulator of CaAR, INF2, is a unique molecule that can at the same time stimulate actin nucleation, elongation, severing and depolymerization (Gurel et al, 2015). We could validate our theoretical prediction, using a mutant INF2 with reduced depolymerization activity.…”

Section: Discussionmentioning

confidence: 99%

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Wales

Schuberth

Aufschnaiter

et al. 2016

eLife

138

186

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Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in response to many physiological cues. CaAR leads to transient immobilization of organelles, drives reorganization of actin during cell cortex repair, cell spreading and wound healing, and induces long-lasting changes in gene expression. Our findings suggest that CaAR acts as fundamental facilitator of cellular adaptations in response to acute signals and stress.DOI: http://dx.doi.org/10.7554/eLife.19850.001

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Section: Discussionmentioning

confidence: 99%

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Wales

Schuberth

Aufschnaiter

et al. 2016

eLife

138

186

View full text Add to dashboard Cite

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“…The presence of the C-terminus in INF2-FFC constructs dampened these negative effects, suggesting the WH2/DAD might participate in nucleation (although this might also reflect the formation of new filaments by C-terminus-dependent filament severing producing new filament ends, see below) [Ramabhadran et al, 2012]. Qualitatively similar to other formins, INF2-FFC slows elongation in the absence of profilin, but accelerates elongation in the presence of profilin [Chhabra and Higgs, 2006; Gurel et al, 2015]. One surprising property found for INF2 was that INF2-FFC also severs actin filaments to near completion in a manner dependent on its C-terminal WH2/DAD, and partially dependent on the conserved I643 and K792 residues of the FH2 domain [Chhabra and Higgs, 2006; Ramabhadran et al, 2012].…”

Section: Effects Of Inf2 On Actin Dynamics In Vitromentioning

confidence: 99%

“…Rather, the combined effects of profilin, INF2, and an adequate supply of ATP result in a steady-state condition of actin filaments that undergo a continual flux of monomer through addition by filament elongation, and loss by filament severing [Gurel et al, 2015] (Fig 2 A).…”

Section: Effects Of Inf2 On Actin Dynamics In Vitromentioning

confidence: 99%

“…(1) Interaction between the DID and DAD hold INF2 in an autoinhibited state. (2) With activation of INF2, ATP-actin associates with the FH2 domain and the WH2-like DAD, with a potential ratio of four actin monomers per INF2 dimer [Gurel et al, 2015]. (3) ATP-actin monomers bound to profilin are recruited by INF2 through interaction of profilin with the FH1 domains, followed by transfer of the monomers to the FH2 domain-bound barbed end.…”

Section: Figurementioning

confidence: 99%

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Inverted formins: A subfamily of atypical formins

2017

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Formins are a family of regulators of actin and microtubule dynamics that are present in almost all eukaryotes. These proteins are involved in many cellular processes, including cytokinesis, stress fiber formation, and cell polarization. Here we review one sub-family of formins, the inverted formins. Inverted formins as a group break several formin stereotypes, having atypical biochemical properties and domain organization, and they have been linked to kidney disease and neuropathy in humans. In this review, we will explore recent research on members of the inverted formin sub-family in mammals, zebrafish, fruit flies, and worms.

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“…Formin family proteins can modulate actin filament dynamics by various means, including actin filament bundling or even severing13, but the most common activities are nucleation of actin filaments and their processive elongation in a profilin-dependent fashion1415. In many cell types, formins are best known for their potential function in driving the assembly of linear actin filaments and bundles in filopodia16171819, although no particular formin is as yet recognized as essential for the formation of these structures2021.…”

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confidence: 99%

FMNL formins boost lamellipodial force generation

et al. 2017

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Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.

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Assembly and Turnover of Short Actin Filaments by the Formin INF2 and Profilin

Cited by 32 publications

References 48 publications

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Inverted formins: A subfamily of atypical formins

FMNL formins boost lamellipodial force generation

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