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Originally published as MBC in Press, 10.1091/mbc.E07-11-1197 on October 15, 2008

Vol. 20, Issue 1, 452-463, January 1, 2009

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RhoE Is Required for Keratinocyte Differentiation and Stratification

Timo Liebig*, Jennifer Erasmus*, Ruba Kalaji*, Derek Davies{dagger}, Gervaise Loirand{ddagger}, Anne Ridley§, and Vania M.M. Braga*

*Molecular Medicine, National Heart and Lung Institute, Imperial College London. SW7 2AZ, London, United Kingdom; {dagger}London Research Institute, Cancer Research UK, WC2A 3PX London, United Kingdom; {ddagger}Institut National de la Santé et de la Recherche Médicale U533, University of Nantes, 44035 Nantes, France; and §King's College London, Randall Division of Cell and Molecular Biophysics, Guy's Campus, London SE1 1UL, United Kingdom

Submitted December 1, 2007; Revised September 26, 2008; Accepted October 3, 2008
Monitoring Editor: Keith E. Mostov

The molecular mechanism via which keratinocyte differentiation assembles multiple layers of cells (stratification) is poorly understood. We describe here a novel function of the Rho family member RhoE as a regulator of epidermal morphogenesis. RhoE protein levels are specifically and transiently up-regulated upon keratinocyte differentiation. RhoE up-regulation requires the activity of Rho kinase (ROCK) I, suggesting that both RhoE and ROCKI are important during keratinocyte differentiation. RhoE overexpression results in a striking enlargement of cell size and the number of stratified cells. In contrast, RhoE depletion induces hyperproliferation and delays initiation of keratinocyte differentiation. Interestingly, up-regulation of RhoE protein is seen primarily in basal, undifferentiated cells, in which commitment to differentiation and stratification takes place. RhoE activation in basal cells negatively modulates integrin adhesion, thereby facilitating detachment from the substratum and migration to form suprabasal layers. Thus, RhoE integrates two processes essential for keratinocyte differentiation and stratification: regulation of proliferative status and integrin adhesion.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-11-1197) on October 15, 2008.

Address correspondence to: Vania Braga (v.braga{at}imperial.ac.uk)






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