AJP - Renal Physiology, Vol 271, Issue 3 579-F587, Copyright © 1996 by American Physiological Society
Extracellular matrix stimulates production and breakdown of inositol phospholipids
A. V. Cybulsky, A. J. McTavish and J. Papillon
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Adhesion of rat glomerular epithelial cells (GEC) to collagen stimulates
production of D-myo-inositol 1,4,5-trisphosphate (IP3) 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 phosphatidylinositol 4,5-bisphosphate (PIP2) and
IP3, 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 IP3 in GEC adherent to ECM is associated with increased
production of PIP2. Moreover, adhesion to ECM increases tyrosine
phosphorylation and membrane association of PLC-gamma 1, which may
facilitate PIP2 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.
