Vol. 12, Issue 10, 3268-3281, October 2001

RhoA-dependent Switch between 21 and 31 Integrins Is Induced by Laminin-5 during Early Stage of HT-29 Cell Differentiation

Stéphanie P. Gout,^* Muriel R. Jacquier-Sarlin,^* Laurence Rouard-Talbot, Patricia Rousselle,^§ and Marc R. Block

 Laboratoire d'Etude de la Différenciation et de l'Adhérence Cellulaires, Unité Mixte de Recherche 5538 Institut Albert Bonniot, La Tronche Cedex, France; and  ^§Institut de Biologie et Chimie des Protéines, Centre National de la Recherche Scientifique, Lyon, France

Integrin-mediated interactions between the basement membrane and epithelial cells control the differentiation of epithelia. We characterized the modulation of adhesive behaviors to basement membrane proteins and of integrin function in the human colon adenocarcinoma HT-29 cell line, which differentiates into enterocytes after the substitution of galactose for glucose in the medium. We demonstrate an increased capability of these cells to adhere to collagen type IV during the early stage of differentiation. This effect occurs without any changes in integrin cell surface expression but rather results from an 21/31 integrin switch, 31 integrin becoming the major collagen receptor. The increase in laminin-5 secretion and deposit on the matrix is a key factor in the mechanism regulating cell adhesion, because it is responsible for the activation of 31 integrin. Furthermore, down-regulation of RhoA GTPase activity occurs during HT-29 cell differentiation and correlates with the activation of the integrin 31. Indeed, C3 transferase, a RhoA GTPase inhibitor, induces a similar 21/31 switch in undifferentiated HT-29 cells. These results indicate that the decrease in RhoA activation is the biochemical mechanism underlying this integrin switch observed during cell differentiation. The physiological relevance of such modulation of integrin activity in the functioning of the crypt-villus axis is discussed.