Author response: Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion

Damiano-Guercio, Julia; Kurzawa, Laëtitia; Mueller, Jan O.; Dimchev, Georgi; Schaks, Matthias; Nemethova, Maria; Pokrant, Thomas; Brühmann, Stefan; Linkner, Joern; Blanchoin, Laurent; Sixt, Michael; Rottner, Klemens; Faix, Jan

doi:10.7554/elife.55351.sa2

Cited by 2 publications

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“…Significantly, FMNL2/3 RNAi also strongly interfered with the spreading increase induced by Arp3 removal in these experiments (Figure 9F), confirming the conclusion that filopodia can indeed promote this process (see above and Supplementary Video 1). We should emphasize that additional actin polymerases have previously been implicated in filopodia formation, foremost of all Ena/VASP family members (Dent et al, 2007), although they are certainly not obligatory for these structures (Damiano-Guercio et al, 2020). It is tempting to speculate that during spreading in the presence of Arp2/3 complex, Ena/VASP proteins are more relevant for the formation of the filopodia formed under these conditions than FMNL2/3 proteins.…”

Section: Acute Arp3 Loss Of Function Increases Expression Of Fmnl Subfamily Formins That Operate In Filopodia Formationmentioning

confidence: 89%

Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation

Dimchev

Lahmann

Koestler

et al. 2021

Front. Cell Dev. Biol.

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The Arp2/3 complex generates branched actin filament networks operating in cell edge protrusion and vesicle trafficking. Here we employ a conditional knockout mouse model permitting tissue- or cell-type specific deletion of the murine Actr3 gene (encoding Arp3). A functional Actr3 gene appeared essential for fibroblast viability and growth. Thus, we developed cell lines for exploring the consequences of acute, tamoxifen-induced Actr3 deletion causing near-complete loss of functional Arp2/3 complex expression as well as abolished lamellipodia formation and membrane ruffling, as expected. Interestingly, Arp3-depleted cells displayed enhanced rather than reduced cell spreading, employing numerous filopodia, and showed little defects in the rates of random cell migration. However, both exploration of new space by individual cells and collective migration were clearly compromised by the incapability to efficiently maintain directionality of migration, while the principal ability to chemotax was only moderately affected. Examination of actin remodeling at the cell periphery revealed reduced actin turnover rates in Arp2/3-deficient cells, clearly deviating from previous sequestration approaches. Most surprisingly, induced removal of Arp2/3 complexes reproducibly increased FMNL formin expression, which correlated with the explosive induction of filopodia formation. Our results thus highlight both direct and indirect effects of acute Arp2/3 complex removal on actin cytoskeleton regulation.

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Section: Acute Arp3 Loss Of Function Increases Expression Of Fmnl Subfamily Formins That Operate In Filopodia Formationmentioning

confidence: 89%

Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation

Dimchev

Lahmann

Koestler

et al. 2021

Front. Cell Dev. Biol.

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Induced Arp2/3 complex depletion increases FMNL2/3 formin expression and filopodia formation

Dimchev

Lahmann

Koestler

et al. 2020

Preprint

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The Arp2/3 complex generates branched actin filament networks operating in cell edge protrusion and vesicle trafficking. Here we employ a novel, conditional knockout mouse model permitting tissue- or cell-type specific deletion of the murine Actr3 gene (encoding Arp3). A functional Actr3 gene appeared essential for fibroblast viability and growth. Thus, we developed cell lines for exploring the consequences of acute, tamoxifen-induced Actr3 deletion causing near-complete loss of Arp/3 complex function as well as abolished lamellipodia formation and membrane ruffling, as expected. However, Arp3-depleted cells displayed enhanced rather than reduced cell spreading, employing numerous filopodia, and showed little defects in individual cell migration. Reduction of collective cell migration as observed for instance in wound healing assays likely derived from defects in maintaining directionality during migration, while the principal ability to chemotax was only moderately affected. Analyses of actin turnover at the cell periphery revealed reduced actin turnover rates in Arp2/3-deficient cells, clearly deviating from previous sequestration approaches. Most surprisingly, induced removal of Arp2/3 complexes reproducibly increased FMNL formin expression, which correlated with the explosive induction of filopodia formation. Our results thus highlight both direct and indirect effects of acute Arp2/3 complex removal on actin cytoskeleton regulation.

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Author response: Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion

Cited by 2 publications

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Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation

Induced Arp2/3 Complex Depletion Increases FMNL2/3 Formin Expression and Filopodia Formation

Induced Arp2/3 complex depletion increases FMNL2/3 formin expression and filopodia formation

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