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A more recent version of this article appeared on February 1, 2005
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Submitted on May 27, 2004
Revised on November 1, 2004
Accepted on November 19, 2004
1-Integrin Orients Epithelial Polarity via Rac1 and Laminin
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*Departments of Anatomy and Biochemistry and Biophysics, School of Medicine, University of California San Francisco, San Francisco, CA 94143; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100 Taiwan; Epithelial Pathobiology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0581
Monitoring Editor: Jean Schwarzbauer
Epithelial cells polarize and orient polarity in response to cell-cell and cell-matrix adhesion. Although there has been much recent progress in understanding the general polarizing machinery of epithelia, it is largely unclear how this machinery is controlled by the extracellular environment. To explore the signals from cell-matrix interactions that control orientation of cell polarity, we have used three-dimensional culture systems in which MDCK cells form polarized, lumen-containing structures. We show that interaction of collagen I with apical 
1-integrins after collagen overlay of a polarized MDCK monolayer induces activation of Rac1, which is required for collagen overlay-induced tubulocyst formation. Cysts, comprised of a monolayer enclosing a central lumen, form after embedding single cells in collagen. In those cultures, addition of a 1-integrin function-blocking antibody to the collagen matrix gives rise to cysts that have defects in the organization of laminin into the basement membrane and have inverted polarity. Normal polarity is restored by either expression of activated Rac1, or the inclusion of excess laminin-1 (LN-1). Taken together, our results suggest a signaling pathway in which the activation of 1-integrins orients the apical pole of polarized cysts via a mechanism that requires Rac1 activation and laminin organization into the basement membrane.
Present address: Epithelial Pathobiology, Department of Surgery, The Vontz Center, University of Cincinnati College of Medicine, 3125 Eden Avenue ML0581, Cincinnati, OH 45267-0581.
||Corresponding author.
E-mail: zegersm{at}ucmail.uc.edu
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