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dc.contributor.authorJackson, Ben
dc.contributor.authorPeyrollier, Karine
dc.contributor.authorPedersen, Esben
dc.contributor.authorBasse, Astrid
dc.contributor.authorKarlsson, Richard
dc.contributor.authorWang, Zhipeng
dc.contributor.authorLefever, Tine
dc.contributor.authorOchsenbein, Alexandra M
dc.contributor.authorSchmidt, Gudula
dc.contributor.authorAktories, Klaus
dc.contributor.authorStanley, Alanna
dc.contributor.authorQuondamatteo, Fabio
dc.contributor.authorLadwein, Markus
dc.contributor.authorRottner, Klemens
dc.contributor.authorvan Hengel, Jolanda
dc.contributor.authorBrakebusch, Cord
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.
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
refterms.dateFOA2018-06-13T00:16:38Z
html.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.


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