Laminin-5-integrin interaction signals through PI 3-kinase and Rac1b to promote assembly of adherens junctions in HT-29 cells
Author:
Chartier Nicolas T.1, Lainé Michèle1, Gout Stéphanie1, Pawlak Géraldine1, Marie Christiane A.1, Matos Paulo2, Block Marc R.1, Jacquier-Sarlin Muriel R.1
Affiliation:
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
Abstract
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 α6 and, to a lesser extent, α3 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.
Publisher
The Company of Biologists
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