Actin Monomers Activate Inverted Formin 2 by Competing with Its Autoinhibitory Interaction

Ramabhadran, Vinay; Hatch, Anna L.; Higgs, Henry N.

doi:10.1074/jbc.m113.472415

Cited by 52 publications

(77 citation statements)

References 40 publications

(47 reference statements)

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“…INF2 assembles into FAs in a contractility-dependent manner during FA maturation rather than during initial FA generation, (42) and FAs in cells lacking INF2 lack actin bundles, this suggests that the role of INF2 in FA maturation is through regulation of FA-associated actin rather than direct effects on FAs. INF2 has a number of activities that could modulate actin at FAs, including the FH1-FH2 domains that polymerize actin, a WH2-like domain at the C terminus (35) that binds actin monomers to regulate autoinhibition, and also mediates filament severing (35,36). INF2 also interacts with and inhibits members of the diaphanous family of formins (37).…”

Section: Discussionmentioning

confidence: 99%

“…INF2 is expressed in cells in two isoforms, one containing a membrane-targeting CAAX-motif that plays a role in mitochondrial fission (34) and a non-CAAX isoform whose function is not well characterized. INF2 is an unusual formin insofar as it contains, in addition to the FH1-FH2 domains that polymerize actin, a WH2-like domain at the C terminus (35) that binds actin monomers to regulate autoinhibition, and also mediates filament severing (35,36). INF2 also interacts with and inhibits members of the diaphanous family of formin proteins (37).…”

Section: Significancementioning

confidence: 99%

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RETRACTED: Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly

Skau

Plotnikov

Doyle

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Actin filaments and integrin-based focal adhesions (FAs) form integrated systems that mediate dynamic cell interactions with their environment or other cells during migration, the immune response, and tissue morphogenesis. How adhesion-associated actin structures obtain their functional specificity is unclear. Here we show that the formin-family actin nucleator, inverted formin 2 (INF2), localizes specifically to FAs and dorsal stress fibers (SFs) in fibroblasts. High-resolution fluorescence microscopy and manipulation of INF2 levels in cells indicate that INF2 plays a critical role at the SF–FA junction by promoting actin polymerization via free barbed end generation and centripetal elongation of an FA-associated actin bundle to form dorsal SF. INF2 assembles into FAs during maturation rather than during their initial generation, and once there, acts to promote rapid FA elongation and maturation into tensin-containing fibrillar FAs in the cell center. We show that INF2 is required for fibroblasts to organize fibronectin into matrix fibers and ultimately 3D matrices. Collectively our results indicate an important role for the formin INF2 in specifying the function of fibrillar FAs through its ability to generate dorsal SFs. Thus, dorsal SFs and fibrillar FAs form a specific class of integrated adhesion-associated actin structure in fibroblasts that mediates generation and remodeling of ECM.

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

RETRACTED: Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly

Skau

Plotnikov

Doyle

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Binding-The role of Capu-tail in nucleation is consistent with recent reports about Diaphanous-related formins (16,18) and INF2 (41) in that the formin tail is a site for monomer binding and, thus, aids the FH2 domain in filament nucleation. The low affinity of the Capu-tail/G-actin interaction is notable when comparing it to other formin tails.…”

Section: The Role Of Formin Tails In Filament Nucleation and G-actinsupporting

confidence: 75%

“…Sequestering this actin binding region is at least part of the mechanism by which KIND inhibits the nucleation activity of Capu (15). Because tail/actin interactions are Ϸ1000-fold weaker than the tail/KIND interaction, we do not expect that actin monomers would effectively compete with this interaction to activate Capu, as reported recently for INF2 (41). Instead, we speculate that Spire binding may be a mode of enhancing the weak monomer binding of the tail, given that binding of each Spire molecule places four WH2 domains in proximity to the Capu-FH2 domain.…”

Section: The Role Of Formin Tails In Filament Nucleation and G-actinmentioning

confidence: 60%

The Role of Formin Tails in Actin Nucleation, Processive Elongation, and Filament Bundling

Vizcarra

Bor

Quinlan

2014

Journal of Biological Chemistry

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Background: Formins build essential actin-based structures. Results: The tails of Cappuccino and other formins contribute to both nucleation and processive filament elongation by binding actin monomers and filaments, respectively. Conclusion: Formin tails tune actin assembly. Their role in processivity was not previously recognized. Significance: Identifying the functions of the tail domain will lead to an understanding of how Capu and other formins function and are regulated.

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“…Whereas, inhibitory Smad (I-Smad) including Smad6 and Smad7 could negatively regulate BMP-Smad signaling pathway (Sartori et al, 2013). Endoplasmic reticulum produces actin monomers that supply the material basis for actin dynamics (Ramabhadran et al, 2013).…”

Section: Aβ-induced Neurodegenerative Stressmentioning

confidence: 99%

Roles of BMP6/7 in Actin Dynamics in Amyloid β-Induced Neurotoxicity

Sun¹,

Zhang²,

Xiao³

2014

PSYCH

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Actin dynamics plays an important role in many physiological functions such as long-term potentiation, neurotransmission, regulatory proteins translocation, ATP cycle, etc. When amyloid β (Aβ)-induced neurotoxicity occurs, the imbalance of actin dynamics leads to dystrophy of dendrites, which is characteristic pathology in Alzheimer's disease (AD). Transient and persistent Aβ neurotoxicity provokes distinct manifestations of actin dynamics and causes opposing effects in AD. It has been shown that bone morphogenetic protein 6/7 (BMP6/7) protects neuronal morphology against Aβ-induced neurotoxicity, and can directly bind to LIM kinase1 (LIMK1), being one part of the upstream regulatory pathway of actin dynamics. This review aims to discuss a potential mechanism of BMPs underlying maintainance of cytoskeletal stabilization in neurite.

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Actin Monomers Activate Inverted Formin 2 by Competing with Its Autoinhibitory Interaction

Cited by 52 publications

References 40 publications

RETRACTED: Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly

RETRACTED: Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly

The Role of Formin Tails in Actin Nucleation, Processive Elongation, and Filament Bundling

Roles of BMP6/7 in Actin Dynamics in Amyloid β-Induced Neurotoxicity

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