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First published online 7 October 2008
doi: 10.1242/jcs.029538

Journal of Cell Science 121, 3561-3569 (2008)
Published by The Company of Biologists 2008
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Research Article

Kazrin regulates keratinocyte cytoskeletal networks, intercellular junctions and differentiation

Lisa M. Sevilla1,2, Rachida Nachat1, Karen R. Groot3 and Fiona M. Watt1,2,*

1 Epithelial Cell Biology Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
2 Wellcome Trust Centre for Stem Cell Research and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
3 National Cancer Research Institute, 61 Lincoln's Inn Fields, PO Box 123, London WC2A 3PX, UK

* Author for correspondence (e-mail: fiona.watt{at}cancer.org.uk)

Accepted 4 August 2008

Kazrin is an evolutionarily conserved protein that is upregulated during keratinocyte terminal differentiation. Kazrin localizes to desmosomes and binds the epidermal cornified envelope protein periplakin. Kazrin overexpression in human epidermal keratinocytes caused profound changes in cell shape, reduced filamentous actin, reorganized keratin filaments, and impaired assembly of intercellular junctions. These effects were attributable to decreased Rho activity in kazrin-overexpressing cells. Kazrin overexpression also stimulated terminal differentiation and reduced clonal growth in culture. Knockdown of kazrin decreased expression of differentiation markers and stimulated proliferation without changing total Rho activity. We conclude that kazrin is a dual regulator of intercellular adhesion and differentiation in keratinocytes and regulates these processes by Rho-dependent and -independent mechanisms.

Key words: Rho GTPases, Cytoskeleton, Desmosomes, Keratinocyte, Terminal differentiation


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