Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein.

Abstract

The peripheral cytoplasm of macrophages is involved in the control of locomotion, secretion and endocytosis, events common to many eukaryotic cells. During these activities, the cortical cytoplasm, which contains numerous actin filaments1,2, appears to undergo reversible gel–sol transformations3: cycles of gelation and solation are demonstrable in suitably prepared macrophage extracts, and the gels contain tangled actin filaments4. These changes in consistency of cytoplasmic actin may regulate motile events in the macrophage periphery. Calcium in micromolar concentrations prevents gelation of crude macrophage cytoplasmic extracts4, providing a possible link to abundant indirect evidence implicating calcium in the regulation of locomotion, secretion and endocytosis5. Similar calcium-sensitive gelation phenomena occur in crude cell extracts from diverse cell types and may have a relevance for control of cell movements in general6–11. Actin gelation results from the cross-linking of actin filaments (F-actin) by other proteins. In macrophages, a high molecular weight actin-binding protein (ABP) is the principal actin cross-linking protein12. Cross-linking of actin by these purified actin-binding proteins, however, is insensitive to changes in the calcium concentration4,12, so that another factor must mediate the expression of a calcium effect. We have now isolated such a calcium-dependent regulatory protein from macrophages and call it gelsolin.