Cholesterol availability modulates myoblast fusion.
The requirement of cholesterol for myoblast fusion has been linked to the primary step in the fusion process, calcium-dependent aggregation (recognition). Inhibition of cholesterol synthesis with 25-hydroxycholesterol or compactin in the absence of exogenous lipid dramatically inhibits calcium-mediated aggregation and concomitant fusion within several hours. Restimulating cholesterol synthesis or supplying exogenous cholesterol rapidly restores aggregation activity. Over this time period, however, the sterol:phospholipid ratio is unaltered, suggesting a local rather than a general membrane cholesterol requirement for the expression of aggregation activity. The aggregation response to a change in sterol availability occurs on a shorter time scale than that required to inhibit the synthesis of the protein(s) with aggregation activity; thus, the cholesterol-requiring step is posttranslational. We suggest that the assembly or maintenance of the aggregation activity depends on a continued local supply of cholesterol.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects*; D002645:Chickens; D003513:Cycloheximide / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives*; D009132:Muscles / Q000166:cytology*; D009281:Naphthalenes / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D014415:Tunicamycin; C012258:mevastatin; D003513:Cycloheximide; D008148:Lovastatin; D002118:Calcium