Myoblast fusion and inositol phospholipid breakdown: causal relationship or coincidence?

The fusion of embryonic chick myoblasts has been examined in culture. Cells were prepared from 12-day-old chick embryonic breast muscle and cultured for 50 h at a Ca2+ concentration in the medium of 10(-7) M. During this period they attain fusion competence. Addition of 1.4 mM-Ca2+ to these cells elicits rapid fusion. Changes in the metabolism of myoblast phospholipids in response to the raised Ca2+ concentration have been examined. Only the inositol phospholipids are affected. Phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate are rapidly broken down and 1,2-diacylglycerol and phosphatidic acid are synthesized. Myoblast fusion has also been found to be stimulated by a factor present in chick embryo extract, probably of neuronal origin. A receptor-mediated mechanism for myoblast fusion is proposed. This envisages the polyphosphoinositides acting as a fusion block, either themselves or by their binding to membrane proteins. The inositol phospholipid breakdown could result in a more fluid membrane and the breakdown products 1,2-diacylglycerol and phosphatidic acid, two known fusogens, could stimulate fusion.