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First published online 10 June 2008
doi: 10.1242/jcs.021717

Journal of Cell Science 121, 2265-2274 (2008)
Published by The Company of Biologists 2008
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Research Article

Association of tetraspanin CD9 with transmembrane TGF{alpha} confers alterations in cell-surface presentation of TGF{alpha} and cytoskeletal organization

Isabella Imhof, Warren J. Gasper and Rik Derynck*

Department of Cell and Tissue Biology, Program in Cell Biology, University of California–San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA

* Author for correspondence (e-mail: rik.derynck{at}ucsf.edu)

Accepted 9 April 2008

Ligand presentation is a major determinant of receptor activation. The epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is activated by growth factors of the transforming growth factor {alpha} (TGF{alpha}) family. The tetraspanin CD9 interacts with transmembrane TGF{alpha} and decreases its ectodomain shedding to release soluble TGF{alpha}. Here we report that CD9 has a role in the maturation of transmembrane TGF{alpha} and its stabilization at the cell surface, and in the cell-surface distribution in polarized epithelial cells. Furthermore, coexpression of CD9 and TGF{alpha} confers changes in cytoskeletal organization with a decrease in actin stress fibers and focal adhesions, and changes in RhoA and Rac1 GTPase activity. These alterations are reversed by blocking EGFR signaling. Finally, we demonstrate changes in cell adhesion and migration resulting from coexpression of TGF{alpha} with CD9. These results provide insight into the role of CD9 in the presentation of TGF{alpha} in epithelial and carcinoma cells, whose physiology is driven by ligand-induced EGFR activation.

Key words: Epithelial cells, Tetraspanin, Transforming growth factor {alpha}


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