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First published online 8 December 2005
doi: 10.1242/jcs.02698

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Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells

Nicolas T. Chartier^1,*, Michèle Lainé^1,*, Stéphanie Gout¹, Géraldine Pawlak¹, Christiane A. Marie¹, Paulo Matos², Marc R. Block¹ and Muriel R. Jacquier-Sarlin^1,

¹ Laboratoire d'Etude de la Différenciation et de l'Adhérence Cellulaires, UMR UJF/CNRS 5538, Institut Albert Bonniot, Faculté de Médecine de Grenoble, Domaine de la Merci, 38706 La Tronche Cedex, France
² Centro de genética Humana, Instituto Nacional de Saùde `Dr Ricardo Jorge' Avenida Padre Cruz, 1649-016 Lisboa, Portugal

Author for correspondence (e-mail: jacquier-sarlin{at}ujf-grenoble.fr)

Accepted 16 September 2005

Human intestinal cell differentiation is mediated by signaling pathways that remain largely undefined. We and others have shown that cell migration and differentiation along the crypt-villus axis is associated with temporal and spatial modulations of the repertoire, as well as with the function of integrins and E-cadherins and their substrates. Cross-talk between integrin and cadherin signaling was previously described and seems to coordinate this differentiation process. Here, we report that engagement of ₆ and, to a lesser extent, ₃ integrin subunits after HT-29 cell adhesion on laminin 5 increases the expression of E-cadherin, which then organizes into nascent adherens junctions. We further identify that phosphoinositide 3-kinase (PI 3-kinase) activation plays a key role in this cross-talk. Indeed, integrin-dependent adhesion on laminin 5 stimulates PI 3-kinase activity. Immunofluorescence and immunoprecipitation experiments revealed that activated PI 3-kinase is recruited at cell-cell contacts. Using LY294002, an inhibitor of PI 3-kinase activity, we found that this activation is essential for E-cadherin connection with the cytoskeleton and for biogenesis of adherens junctions. Finally, we demonstrated that PI 3-kinase could signal through Rac1b activation to control adherens junction assembly. Our results provide a mechanistic insight into integrin-cadherin cross-talk and identify a novel role for PI 3-kinase in the establishment of adherens junctions.

Key words: Adhesion-mediated signaling, Adherens junctions, Integrins, Extracellular matrix, E-cadherin, Rac 1, Phosphoinositide 3-kinase

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