Order of events leading to surface immunoglobulin capping: analysis of a transmembrane signal.

Capping provides a rapid assay for the transduction of 1 type of membrane signal generated by the cross-linking of cell surface receptors. The order of the steps comprising this signal was determined by employing reversible inhibitors of lymphocyte surface Ig capping in a sequential incubation protocol. The results demonstrated that surface Ig cross-linking leads to capping by a linear series of discrete events. Although the steps inhibited by the calcium ionophore A23187 and the tranquilizer chlorpromazine could not be distinguished, other agents also thought to influence calcium distribution in the cell acted at different steps. The order of inhibited steps was shown to be: 1) hydrocortisone; 2) calcium ionophore or chlorpromazine; 3) cytochalasins; 4) dibucaine; 5) propranolol; 6) fluoride; 7) azide. These results suggest a model wherein cross-linked membrane Ig aggregates engage the preassembled microfilament system by means of a calcium-dependent linkage. Further calcium redistribution within the cell then leads to an energy-consuming contractile event.