Extracellular matrix stimulates production and breakdown of inositol phospholipids
Cybulsky, A.V.; McTavish, A.J.; Papillon, J.
American Journal of Physiology 271(3 Pt 2): F579-F587
1996
ISSN/ISBN: 0002-9513 PMID: 8853419 Document Number: 455831
Adhesion of rat glomerular epithelial cells (GEC) to collagen stimulates production of D-myo-inositol 1,4,5-trisphosphate (IP-3) and 1,2-diacylglycerol. This process is mediated via beta-1-integrins, and it modulates GEC proliferation. In this study, we address the changes in inositol-lipid turnover induced by GEC adhesion to extracellular matrix (ECM). The masses of both phosphatidyhnositol 4,5-bisphosphate (PIP-2) and IP-3, as well as (3H)inositol phosphates, were increased in GEC adherent to collagen, compared with plastic substratum. Phosphatidylinositol-4-phosphate (PIP) 5-kinase activity was predominantly membrane associated and was enhanced in GEC on collagen. Phospholipase C (PLC) activity and PLC-gamma-1 protein were increased in membrane fractions of GEC adherent to collagen, compared with plastic. Stable overexpression of PLC-gamma-1 in GEC amplified the effect of ECM on the production of (3H)inositol phosphates. In addition, the PLC-gamma-1 that was membrane associated in collagen-adherent GEC was tyrosine phosphorylated. Thus production of IP-3 in GEC adherent to ECM is associated with increased production of PIP-2. Moreover, adhesion to ECM increases tyrosine phosphorylation and membrane association of PLC-gamma-1, which may facilitate PIP-2 hydrolysis by increasing the catalytic activity of PLC-gamma-1 and the proximity of PLC-gamma-1 and its substrate. Understanding the process of ECM-induced inositol lipid production and breakdown in GEC may provide insights into the regulation of GEC proliferation and differentiated functions in normal conditions and during glomerular injury.