RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/213811
Title:
RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes.
Authors:
Jackson, Ben; Peyrollier, Karine; Pedersen, Esben; Basse, Astrid; Karlsson, Richard; Wang, Zhipeng; Lefever, Tine; Ochsenbein, Alexandra M; Schmidt, Gudula; Aktories, Klaus; Stanley, Alanna; Quondamatteo, Fabio; Ladwein, Markus; Rottner, Klemens; van Hengel, Jolanda; Brakebusch, Cord
Abstract:
RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratinocyte-restricted deletion of the RhoA gene. Despite a severe reduction of cofilin and myosin light chain (MLC) phosphorylation, these mice showed normal skin development. Primary RhoA-null keratinocytes, however, displayed an increased percentage of multinucleated cells, defective maturation of cell-cell contacts. Furthermore we observed increased cell spreading due to impaired RhoA-ROCK (Rho-associated protein kinase)-MLC phosphatase-MLC-mediated cell contraction, independent of Rac1. Rho-inhibiting toxins further increased multinucleation of RhoA-null cells but had no significant effect on spreading, suggesting that RhoB and RhoC have partially overlapping functions with RhoA. Loss of RhoA decreased directed cell migration in vitro caused by reduced migration speed and directional persistence. These defects were not related to the decreased cell contraction and were independent of ROCK, as ROCK inhibition by Y27632 increased directed migration of both control and RhoA-null keratinocytes. Our data indicate a crucial role for RhoA and contraction in regulating cell spreading and a contraction-independent function of RhoA in keratinocyte migration. In addition, our data show that RhoA is dispensable for skin development.
Affiliation:
Biomedical Institute, BRIC, University of Copenhagen, 2200 Copenhagen, Denmark.
Citation:
RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. 2011, 22 (5):593-605 Mol. Biol. Cell
Journal:
Molecular biology of the cell
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10033/213811
DOI:
10.1091/mbc.E09-10-0859
PubMed ID:
21209320
Type:
Article
Language:
en
ISSN:
1939-4586
Appears in Collections:
Publications of RG Cytoskeleton Dynamics (CYD)

Full metadata record

DC FieldValue Language
dc.contributor.authorJackson, Benen
dc.contributor.authorPeyrollier, Karineen
dc.contributor.authorPedersen, Esbenen
dc.contributor.authorBasse, Astriden
dc.contributor.authorKarlsson, Richarden
dc.contributor.authorWang, Zhipengen
dc.contributor.authorLefever, Tineen
dc.contributor.authorOchsenbein, Alexandra Men
dc.contributor.authorSchmidt, Gudulaen
dc.contributor.authorAktories, Klausen
dc.contributor.authorStanley, Alannaen
dc.contributor.authorQuondamatteo, Fabioen
dc.contributor.authorLadwein, Markusen
dc.contributor.authorRottner, Klemensen
dc.contributor.authorvan Hengel, Jolandaen
dc.contributor.authorBrakebusch, Corden
dc.date.accessioned2012-03-01T16:01:13Z-
dc.date.available2012-03-01T16:01:13Z-
dc.date.issued2011-03-
dc.identifier.citationRhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. 2011, 22 (5):593-605 Mol. Biol. Cellen
dc.identifier.issn1939-4586-
dc.identifier.pmid21209320-
dc.identifier.doi10.1091/mbc.E09-10-0859-
dc.identifier.urihttp://hdl.handle.net/10033/213811-
dc.description.abstractRhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratinocyte-restricted deletion of the RhoA gene. Despite a severe reduction of cofilin and myosin light chain (MLC) phosphorylation, these mice showed normal skin development. Primary RhoA-null keratinocytes, however, displayed an increased percentage of multinucleated cells, defective maturation of cell-cell contacts. Furthermore we observed increased cell spreading due to impaired RhoA-ROCK (Rho-associated protein kinase)-MLC phosphatase-MLC-mediated cell contraction, independent of Rac1. Rho-inhibiting toxins further increased multinucleation of RhoA-null cells but had no significant effect on spreading, suggesting that RhoB and RhoC have partially overlapping functions with RhoA. Loss of RhoA decreased directed cell migration in vitro caused by reduced migration speed and directional persistence. These defects were not related to the decreased cell contraction and were independent of ROCK, as ROCK inhibition by Y27632 increased directed migration of both control and RhoA-null keratinocytes. Our data indicate a crucial role for RhoA and contraction in regulating cell spreading and a contraction-independent function of RhoA in keratinocyte migration. In addition, our data show that RhoA is dispensable for skin development.en
dc.language.isoenen
dc.subject.meshActin Depolymerizing Factorsen
dc.subject.meshAnimalsen
dc.subject.meshCell Counten
dc.subject.meshCell Differentiationen
dc.subject.meshCell Movementen
dc.subject.meshCytokinesisen
dc.subject.meshEpidermisen
dc.subject.meshFocal Adhesionsen
dc.subject.meshGene Deletionen
dc.subject.meshGiant Cellsen
dc.subject.meshIntercellular Junctionsen
dc.subject.meshKeratinocytesen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMiceen
dc.subject.meshMyosin Light Chainsen
dc.subject.meshMyosin-Light-Chain Phosphataseen
dc.subject.meshOrgan Specificityen
dc.subject.meshPhosphorylationen
dc.subject.meshSkinen
dc.subject.meshStress Fibersen
dc.subject.meshWound Healingen
dc.subject.meshrac1 GTP-Binding Proteinen
dc.subject.meshrho-Associated Kinasesen
dc.subject.meshrhoA GTP-Binding Proteinen
dc.titleRhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes.en
dc.typeArticleen
dc.contributor.departmentBiomedical Institute, BRIC, University of Copenhagen, 2200 Copenhagen, Denmark.en
dc.identifier.journalMolecular biology of the cellen

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