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

(2011) MOLECULAR BIOLOGY OF THE CELL. 22(5). p.593-605
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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.
Keywords
MEMBRANE PROTRUSIONS, POLARITY, CELL-MIGRATION, ADHESION, CDC42, RAC, GTPASES, ROCK, ESTABLISHMENT, TURNOVER

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Chicago
Jackson, Ben, Karine Peyrollier, Esben Pedersen, Astrid Basse, Richard Karlsson, Zhipeng Wang, Tine Lefever, et al. 2011. “RhoA Is Dispensable for Skin Development, but Crucial for Contraction and Directed Migration of Keratinocytes.” Molecular Biology of the Cell 22 (5): 593–605.
APA
Jackson, B., Peyrollier, K., Pedersen, E., Basse, A., Karlsson, R., Wang, Z., Lefever, T., et al. (2011). RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. MOLECULAR BIOLOGY OF THE CELL, 22(5), 593–605.
Vancouver
1.
Jackson B, Peyrollier K, Pedersen E, Basse A, Karlsson R, Wang Z, et al. RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes. MOLECULAR BIOLOGY OF THE CELL. 2011;22(5):593–605.
MLA
Jackson, Ben, Karine Peyrollier, Esben Pedersen, et al. “RhoA Is Dispensable for Skin Development, but Crucial for Contraction and Directed Migration of Keratinocytes.” MOLECULAR BIOLOGY OF THE CELL 22.5 (2011): 593–605. Print.
@article{1192676,
  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.},
  author       = {Jackson, Ben and Peyrollier, Karine and Pedersen, Esben and Basse, Astrid and Karlsson, Richard and Wang, Zhipeng  and Lefever, Tine and Ochsenbein, Alexandra M and Schmidt, Gudula and Aktories, Klaus and Stanley, Alanna and Quondamatteo, Fabio and Ladwein, Markus and Rottner, Klemens and van Hengel, Jolanda and Brakebusch, Cord},
  issn         = {1059-1524},
  journal      = {MOLECULAR BIOLOGY OF THE CELL},
  keyword      = {MEMBRANE PROTRUSIONS,POLARITY,CELL-MIGRATION,ADHESION,CDC42,RAC,GTPASES,ROCK,ESTABLISHMENT,TURNOVER},
  language     = {eng},
  number       = {5},
  pages        = {593--605},
  title        = {RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes},
  url          = {http://dx.doi.org/10.1091/mbc.E09-10-0859},
  volume       = {22},
  year         = {2011},
}

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