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MBC in Press, published online ahead of print October 15, 2008
Mol. Biol. Cell 10.1091/mbc.E07-11-1197

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Submitted on December 1, 2007
Revised on September 26, 2008
Accepted on October 3, 2008

RhoE Is Required for Keratinocyte Differentiation and Stratification

Timo Liebig,* Jennifer Erasmus,* Ruba Kalaji,* Derek Davies,{dagger} Gervaise Loirand,{ddagger} Anne Ridley,{sect} and Vania 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}INSERM U533, University of Nantes, 44035 Nantes, France; {sect}King’s College London, Randall Division of Cell and Molecular Biophysics, Guy’s Campus, London SE1 1UL, United Kingdom

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 ROCKI, 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 hyper-proliferation 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.

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






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