Abbreviations used : ERK, extracellular signal-regulated kinase ; ET-1, endothelin-1 ; ETB-R, endothelin receptor subtype B ; FAK, focal adhesion kinase ; FITC, fluorescein isothiocyanate ; PBS, phosphate-buffered saline ; SDS, sodium dodecyl sulfate.
Requirement of Caveolae Microdomains in Extracellular Signal-Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin-1 in Primary Astrocytes
Article first published online: 18 JAN 2002
Journal of Neurochemistry
Volume 72, Issue 1, pages 120–128, January 1999
How to Cite
Teixeira, A., Chaverot, N., Schröder, C., Strosberg, A. D., Couraud, P.-O. and Cazaubon, S. (1999), Requirement of Caveolae Microdomains in Extracellular Signal-Regulated Kinase and Focal Adhesion Kinase Activation Induced by Endothelin-1 in Primary Astrocytes. Journal of Neurochemistry, 72: 120–128. doi: 10.1046/j.1471-4159.1999.0720120.x
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Primary astrocyte;
- Extracellular signal-regulated kinase;
- Focal adhesion kinase;
Abstract : Endothelin-1 (ET-1) mitogenic activity in astrocytes is mediated by the activation of the extracellular signal-regulated kinase (ERK) pathway together with the Rho-dependent activation of the focal adhesion kinase (FAK) pathway. To clarify the mechanisms responsible for the coordinate activation of both pathways in the ET-1 signal propagation, the involvement of caveolae microdomains, suggested to play a role in signal transduction, was evaluated. In this study, it is reported that caveolae of primary astrocytes are enriched in endothelin receptor (ETB-R). Furthermore, signaling molecules such as the adaptor proteins Shc and Grb2, and the small G protein Rho, also reside within these microdomains. Selective disassembly of caveolae by filipin III impairs the ET-1-induced tyrosine phosphorylation of proteins including ERK and FAK. In agreement with these observations, astrocytes pretreated with filipin III also failed to form stress fibers and focal adhesions and did not undergo the associated morphological changes in response to ET-1. This study reveals that structural integrity of caveolae is necessary for the adhesion-dependent mitogenic signals induced by ET-1 in astrocytes, through compartmentation of ETB-R with the upstream signaling molecules of the ERK and FAK pathways.