Lysophosphatidic acid promotes survival and differentiation of rat Schwann cells.
Lysophosphatidic acid (LPA; 1-acyl-sn-glycerol-3-phosphate), an abundant constituent of serum, mediates multiple biological responses via G protein-coupled serpentine receptors. Schwann cells express the LPA receptors (Edg receptors), which, once activated, have the potential to signal through G(alphai) to activate p21(ras) and phosphatidylinositol 3-kinase, through G(alphaq) to activate phospholipase C, or through G(q12/13) to activate the Rho pathway. We found that the addition of serum or LPA to serum-starved Schwann cells rapidly (10 min) induced the appearance of actin stress fibers via a Rho-mediated pathway. Furthermore, LPA was able to rescue Schwann cells from apoptosis in a G(alphai)/phosphatidylinositol 3-kinase/MEK/MAPK-dependent manner. In addition, LPA increased the expression of myelin protein P(0) in Schwann cells in a Galpha(i)-independent manner but dependent on protein kinase C. By means of pharmacological and overexpression approaches, we found that the novel isozyme protein kinase Cdelta was required for myelin P(0) expression. Thus, the multiple effects of LPA in Schwann cells (actin reorganization, survival, and myelin gene expression) appear to be mediated through the different G protein-dependent pathways activated by the LPA receptor.
Li
Yiwen
Y
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Gonzalez
Marco I
MI
Meinkoth
Judy L
JL
Field
Jeffrey
J
Kazanietz
Marcelo G
MG
Tennekoon
Gihan I
GI
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004789:Enzyme Activation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D005799:Genes, Dominant; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009186:Myelin Sheath / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D015500:Chloramphenicol O-Acetyltransferase; D019869:Phosphatidylinositol 3-Kinases; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D016283:Proto-Oncogene Proteins p21(ras)