FMNL formins boost lamellipodial force generation

Frieda Kage; Moritz Winterhoff; Vanessa Dimchev; Jan Mueller; Tobias Thalheim; Anika Freise; Stefan Brühmann; Jana Kollasser; Jennifer Block; Georgi A Dimchev; Matthias Geyer; Hans-Joachim Schnittler; Cord Brakebusch; Theresia E B Stradal; Marie-France Carlier; Michael Sixt; Josef Käs; Jan Faix; Klemens Rottner

doi:10.1038/ncomms14832

FMNL formins boost lamellipodial force generation

Frieda Kage, Moritz Winterhoff, Vanessa Dimchev, Jan Mueller, Tobias Thalheim, Anika Freise, Stefan Brühmann, Jana Kollasser, Jennifer Block, Georgi A Dimchev, Matthias Geyer, Hans-Joachim Schnittler, Cord Brakebusch, Theresia E B Stradal, Marie-France Carlier, Michael Sixt, Josef Käs, Jan Faix, Klemens Rottner

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Abstract

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.

Originalsprog	Engelsk
Artikelnummer	14832
Tidsskrift	Nature Communications
Vol/bind	8
Antal sider	16
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms14832
Status	Udgivet - 22 mar. 2017

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10.1038/ncomms14832Licens: CC BY

FMNL formins boost lamellipodial force generationForlagets udgivne version, 9,08 MBLicens: CC BY

Citationsformater

Kage, F., Winterhoff, M., Dimchev, V., Mueller, J., Thalheim, T., Freise, A., Brühmann, S., Kollasser, J., Block, J., Dimchev, G. A., Geyer, M., Schnittler, H.-J., Brakebusch, C., Stradal, T. E. B., Carlier, M.-F., Sixt, M., Käs, J., Faix, J., & Rottner, K. (2017). FMNL formins boost lamellipodial force generation. Nature Communications, 8, Artikel 14832. https://doi.org/10.1038/ncomms14832

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title = "FMNL formins boost lamellipodial force generation",

abstract = "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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T1 - FMNL formins boost lamellipodial force generation

AU - Kage, Frieda

AU - Winterhoff, Moritz

AU - Dimchev, Vanessa

AU - Mueller, Jan

AU - Thalheim, Tobias

AU - Freise, Anika

AU - Brühmann, Stefan

AU - Kollasser, Jana

AU - Block, Jennifer

AU - Dimchev, Georgi A

AU - Geyer, Matthias

AU - Schnittler, Hans-Joachim

AU - Brakebusch, Cord

AU - Stradal, Theresia E B

AU - Carlier, Marie-France

AU - Sixt, Michael

AU - Käs, Josef

AU - Faix, Jan

AU - Rottner, Klemens

PY - 2017/3/22

Y1 - 2017/3/22

N2 - 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.

AB - 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.

KW - Journal Article

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DO - 10.1038/ncomms14832

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SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

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ER -

FMNL formins boost lamellipodial force generation

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