Cholesterol availability modulates myoblast fusion.

Abstract

The cholesterol requirement for myoblast fusion has been linked to the primary step in the fusion process, Ca-dependent aggregation (recognition). Inhibition of cholesterol synthesis [in a chick embryo breast muscle system] with 25-hydroxycholesterol or compactin in the absence of exogenous lipid dramatically inhibits Ca-mediated aggregation and concomitant fusion within several h. Restimulating cholesterol synthesis or supplying exogenous cholesterol rapidly restores aggregation activity. Over this time period, 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, the cholesterol-requiring step is posttranslational. Presumably the assembly or maintenance of the aggregation activity depends on a continued local supply of cholesterol.