RhoA-dependent switch between alpha2beta1 and alpha3beta1 integrins is induced by laminin-5 during early stage of HT-29 cell differentiation.
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 alpha2beta1/alpha3beta1 integrin switch, alpha3beta1 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 alpha3beta1 integrin. Furthermore, down-regulation of RhoA GTPase activity occurs during HT-29 cell differentiation and correlates with the activation of the integrin alpha3beta1. Indeed, C3 transferase, a RhoA GTPase inhibitor, induces a similar alpha2beta1/alpha3beta1 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.
Gout
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SP
Laboratoire d'Etude de la Différenciation et de l'Adhérence Cellulaires, Unité Mixte de Recherche 5538 Institut Albert Bonniot, La Tronche Cedex, France.
Jacquier-Sarlin
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MR
Rouard-Talbot
L
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Rousselle
P
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Block
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MR
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D019073:HT29 Cells / Q000166:cytology; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D038981:Receptors, Collagen; D015398:Signal Transduction / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D005947:Glucose; D039201:Integrin alpha3beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D038981:Receptors, Collagen; D020742:rhoA GTP-Binding Protein; D000097794:Kalinin