Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation.

2.50
Hdl Handle:
http://hdl.handle.net/10033/306170
Title:
Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation.
Authors:
Steffen, Anika; Ladwein, Markus; Dimchev, Georgi A; Hein, Anke; Schwenkmezger, Lisa; Arens, Stefan; Ladwein, Kathrin I; Margit Holleboom, J; Schur, Florian; Victor Small, J; Schwarz, Janett; Gerhard, Ralf; Faix, Jan; Stradal, Theresia E B; Brakebusch, Cord; Rottner, Klemens
Abstract:
Cell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.
Affiliation:
Institute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, D-53115 Bonn, Germany.
Citation:
Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. 2013, 126 (Pt 20):4572-88 J. Cell. Sci.
Journal:
Journal of cell science
Issue Date:
15-Oct-2013
URI:
http://hdl.handle.net/10033/306170
DOI:
10.1242/jcs.118232
PubMed ID:
23902686
Type:
Article
Language:
en
ISSN:
1477-9137
Appears in Collections:
Publications of RG Cytoskeleton Dynamics (CYD)

Full metadata record

DC FieldValue Language
dc.contributor.authorSteffen, Anikaen
dc.contributor.authorLadwein, Markusen
dc.contributor.authorDimchev, Georgi Aen
dc.contributor.authorHein, Ankeen
dc.contributor.authorSchwenkmezger, Lisaen
dc.contributor.authorArens, Stefanen
dc.contributor.authorLadwein, Kathrin Ien
dc.contributor.authorMargit Holleboom, Jen
dc.contributor.authorSchur, Florianen
dc.contributor.authorVictor Small, Jen
dc.contributor.authorSchwarz, Janetten
dc.contributor.authorGerhard, Ralfen
dc.contributor.authorFaix, Janen
dc.contributor.authorStradal, Theresia E Ben
dc.contributor.authorBrakebusch, Corden
dc.contributor.authorRottner, Klemensen
dc.date.accessioned2013-12-03T15:16:23Z-
dc.date.available2013-12-03T15:16:23Z-
dc.date.issued2013-10-15-
dc.identifier.citationRac function is crucial for cell migration but is not required for spreading and focal adhesion formation. 2013, 126 (Pt 20):4572-88 J. Cell. Sci.en
dc.identifier.issn1477-9137-
dc.identifier.pmid23902686-
dc.identifier.doi10.1242/jcs.118232-
dc.identifier.urihttp://hdl.handle.net/10033/306170-
dc.description.abstractCell migration is commonly accompanied by protrusion of membrane ruffles and lamellipodia. In two-dimensional migration, protrusion of these thin sheets of cytoplasm is considered relevant to both exploration of new space and initiation of nascent adhesion to the substratum. Lamellipodium formation can be potently stimulated by Rho GTPases of the Rac subfamily, but also by RhoG or Cdc42. Here we describe viable fibroblast cell lines genetically deficient for Rac1 that lack detectable levels of Rac2 and Rac3. Rac-deficient cells were devoid of apparent lamellipodia, but these structures were restored by expression of either Rac subfamily member, but not by Cdc42 or RhoG. Cells deficient in Rac showed strong reduction in wound closure and random cell migration and a notable loss of sensitivity to a chemotactic gradient. Despite these defects, Rac-deficient cells were able to spread, formed filopodia and established focal adhesions. Spreading in these cells was achieved by the extension of filopodia followed by the advancement of cytoplasmic veils between them. The number and size of focal adhesions as well as their intensity were largely unaffected by genetic removal of Rac1. However, Rac deficiency increased the mobility of different components in focal adhesions, potentially explaining how Rac - although not essential - can contribute to focal adhesion assembly. Together, our data demonstrate that Rac signaling is essential for lamellipodium protrusion and for efficient cell migration, but not for spreading or filopodium formation. Our findings also suggest that Rac GTPases are crucial to the establishment or maintenance of polarity in chemotactic migration.en
dc.language.isoenen
dc.rightsArchived with thanks to Journal of cell scienceen
dc.titleRac function is crucial for cell migration but is not required for spreading and focal adhesion formation.en
dc.typeArticleen
dc.contributor.departmentInstitute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, D-53115 Bonn, Germany.en
dc.identifier.journalJournal of cell scienceen
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