Secretion of protease nexin-1 by C6 glioma cells is under the control of a heterotrimeric G protein, G sub(o1)

• Published in: The Journal of biological chemistry 1996-12, Vol.271 (49), p.31508-31516
• Main Authors: Lagriffoul, A, Charpentier, N, Carrette, J, Tougard, C, Bockaert, J, Homburger, V
• Format: Article
• Language: English
• ISSN: 0021-9258

Heterotrimeric G sub(o) proteins have recently been described as regulators of vesicular traffic. The G sub(o) alpha gene encodes, by alternative splicing, two G sub(o) alpha polypeptides, G sub(o1) alpha and G sub(o2) alpha . By immunofluorescence and electron microscopy, we detected G sub(o1) alpha on the membrane of small intracellular vesicles in C6 glioma cells. After stable transfection of these cells, overexpression of G sub(o1) alpha but not G sub(o2) alpha was followed by a rise in the secretion of a serine protease inhibitor, protease nexin-1 (PN-1). This secretion was enhanced as a function of the amount of expressed G sub(o1) alpha . Metabolic cell labeling indicated that this increase in PN-1 secretion was not the result of an enhancement in PN-1 biosynthesis or a decrease in it uptake, but revealed a potential role of G sub(o1) alpha in the regulation of vesicular PN-1 trafficking. Furthermore, activators of G sub(o) proteins, mastoparan and a peptide derived from the amino terminus of the growth cone-associated protein GAP43, increased PN-1 secretion in parental and G sub(o1) alpha -overexpressing cells. Brefeldin A, an inhibitor of vesicular traffic, inhibited both basal and mastoparan-stimulated PN-1 secretions. These results indicate, that in C6 glioma cells, PN-1 secretion could be regulated by both G sub(o1) alpha expression and activation.