K252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a fusion-capable state

K252a, an indrocarbazole derivative and protein kinase inhibitor, is report ed to promote myogenic differentiation in C2 mouse myoblasts. We examined t he effects of K252a on QM-RSV cells, quail myoblasts transformed with a tem perature-sensitive mutant of Rous sarcoma virus. K252a promoted myotube for mation of QM-RSV cells. Presumptive QM-RSV cells also formed multinucleated cells when exposed to K252a. However, the expression of myogenin, a muscle regulatory factor, was not stimulated in the presence of the drug, suggest ing that it promotes membrane fusion but not myogenic differentiation. To c onfirm the promotion of membrane fusion by K252a, presumptive C2 cells, whi ch are strongly resistant to HVJ-mediated cell fusion, were fused by HVJ (S endai virus) after K252a treatment. Presumptive C2 cells treated with K252a fused with HVJ, demonstrating that K252a causes the cells to enter a fusio n-capable state. The amount of membrane cholesterol, a factor that decrease s membrane fluidity, fell in K252a-treated C2 cells. The results suggest th at a decrease of membrane cholesterol is a cause of the change that renders myoblast membrane susceptible to fusion in the presence of K252a. (C) 2001 Academic Press.