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Requirement of Caveolae Microdomains in Extracellular Signal‐Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin‐1 in Primary Astrocytes
Author(s) -
Teixeira Alexandra,
Chaverot Nathalie,
Schröder Christian,
Strosberg A. Donny,
Couraud PierreOlivier,
Cazaubon Sylvie
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720120.x
Subject(s) - caveolae , microbiology and biotechnology , focal adhesion , extracellular , kinase , chemistry , signal transduction , biology
: Endothelin‐1 (ET‐1) mitogenic activity in astrocytes ismediated by the activation of the extracellular signal‐regulated kinase (ERK)pathway together with the Rho‐dependent activation of the focal adhesionkinase (FAK) pathway. To clarify the mechanisms responsible for the coordinateactivation of both pathways in the ET‐1 signal propagation, the involvement ofcaveolae microdomains, suggested to play a role in signal transduction, wasevaluated. In this study, it is reported that caveolae of primary astrocytesare enriched in endothelin receptor (ET B ‐R). Furthermore, signalingmolecules such as the adaptor proteins Shc and Grb2, and the small G proteinRho, also reside within these microdomains. Selective disassembly of caveolaeby filipin III impairs the ET‐1‐induced tyrosine phosphorylation of proteinsincluding ERK and FAK. In agreement with these observations, astrocytespretreated with filipin III also failed to form stress fibers and focaladhesions and did not undergo the associated morphological changes in responseto ET‐1. This study reveals that structural integrity of caveolae is necessaryfor the adhesion‐dependent mitogenic signals induced by ET‐1 in astrocytes,through compartmentation of ET B ‐R with the upstream signaling molecules of the ERK and FAK pathways.