Connection between integrins and cell activation in rat adrenal glomerulosa cells: a role for Arg-Gly-Asp peptide in the activation of the p42/p44(mapk) pathway and intracellular calcium.
Integrins are responsible for adhesion and activation of several intracellular cascades. The present study was aimed at determining whether the interaction between fibronectin and integrins could generate pathways involved in physiological functions of rat adrenal glomerulosa cells. Immunofluorescence studies and adhesion assays showed that fibronectin was the best matrix in promoting the formation of focal adhesion. Binding of glomerulosa cells to fibronectin, but not to collagen I or poly-L-lysine, involved the integrin-binding sequence Arg-Gly-Asp (RGD). Activation of glomerulosa cells with Arg-Gly-Asp-Ser (RGDS) induced an increase in [Ca(2+)](i), whereas fibronectin triggered a release of Ca(2+) from InsP(3)-sensitive Ca(2+) stores. Aldosterone secretion induced by ACTH, angiotensin II, and RGDS and proliferation were improved on fibronectin, compared with poly-L-lysine. The RGDS peptide induced a transient increase in the activity of the p42/p44(mapk), independent of phosphatidylinositol-3 kinase and protein kinase C. Integrins alpha(5) and alpha(V) as well as their fibronectin receptor partners beta(1) and beta(3), were identified. These results suggest that in rat adrenal glomerulosa cells, binding of the alpha(5)beta(1), alpha(v)beta(1), or alpha(v)beta(3) integrins to fibronectin is involved in the generation of two important signaling events, increase in intracellular calcium, and activation of the p42/p44(mapk) cascade, leading to cell proliferation and aldosterone secretion.
Campbell
Shirley
S
Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
Otis
Melissa
M
Côté
Mylène
M
Gallo-Payet
Nicole
N
Payet
Marcel Daniel
MD
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D039482:Integrin alpha5 / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans
D005353:Fibronectins; D039482:Integrin alpha5; D039564:Integrin alphaV; D019012:Integrin beta1; D039661:Integrin beta3; D016023:Integrins; D009842:Oligopeptides; D000450:Aldosterone; C047981:arginyl-glycyl-aspartic acid; C046617:arginyl-glycyl-aspartyl-serine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium