2.50
Hdl Handle:
http://hdl.handle.net/10033/620893
Title:
FMNL formins boost lamellipodial force generation.
Authors:
Kage, Frieda; Winterhoff, Moritz; Dimchev, Vanessa; Mueller, Jan; Thalheim, Tobias; Freise, Anika; Brühmann, Stefan; Kollasser, Jana; Block, Jennifer; Dimchev, Georgi; Geyer, Matthias; Schnittler, Hans-Joachim; Brakebusch, Cord; Stradal, Theresia E B; Carlier, Marie-France; Sixt, Michael; Käs, Josef; Faix, Jan; Rottner, Klemens ( 0000-0003-4244-4198 )
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.
Citation:
FMNL formins boost lamellipodial force generation. 2017, 8:14832 Nat Commun
Journal:
Nature communications
Issue Date:
22-Mar-2017
URI:
http://hdl.handle.net/10033/620893
DOI:
10.1038/ncomms14832
PubMed ID:
28327544
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of the department of cell biology (ZBIO); publications of the Research group: molecular cell biology (MZBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKage, Friedaen
dc.contributor.authorWinterhoff, Moritzen
dc.contributor.authorDimchev, Vanessaen
dc.contributor.authorMueller, Janen
dc.contributor.authorThalheim, Tobiasen
dc.contributor.authorFreise, Anikaen
dc.contributor.authorBrühmann, Stefanen
dc.contributor.authorKollasser, Janaen
dc.contributor.authorBlock, Jenniferen
dc.contributor.authorDimchev, Georgien
dc.contributor.authorGeyer, Matthiasen
dc.contributor.authorSchnittler, Hans-Joachimen
dc.contributor.authorBrakebusch, Corden
dc.contributor.authorStradal, Theresia E Ben
dc.contributor.authorCarlier, Marie-Franceen
dc.contributor.authorSixt, Michaelen
dc.contributor.authorKäs, Josefen
dc.contributor.authorFaix, Janen
dc.contributor.authorRottner, Klemensen
dc.date.accessioned2017-04-07T14:44:37Z-
dc.date.available2017-04-07T14:44:37Z-
dc.date.issued2017-03-22-
dc.identifier.citationFMNL formins boost lamellipodial force generation. 2017, 8:14832 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid28327544-
dc.identifier.doi10.1038/ncomms14832-
dc.identifier.urihttp://hdl.handle.net/10033/620893-
dc.description.abstractMigration 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleFMNL formins boost lamellipodial force generation.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr.7, 38124 Braunschweig, Germany.en
dc.identifier.journalNature communicationsen

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