Calreticulin Couples Calcium Release and Calcium Influx in Integrin-mediated Calcium Signaling

摘要

The engagement of integrin α7 in E63 skeletal muscle cells by laminin or anti-α7 antibodies triggered transient elevations in the intracellular free Ca2+ concentration that resulted from both inositol triphosphate-evoked Ca2+ release from intracellular stores and extracellular Ca2+ influx through voltage-gated, L-type Ca2+ channels. The extracellular domain of integrin α7 was found to associate with both ectocalreticulin and dihydropyridine receptor on the cell surface. Calreticulin appears to also associate with cytoplasmic domain of integrin α7 in a manner highly dependent on the cytosolic Ca2+ concentration. It appeared that intracellular Ca2+ release was a prerequisite for Ca2+ influx and that calreticulin associated with the integrin cytoplasmic domain mediated the coupling of between the Ca2+ release and Ca2+ influx. These findings suggest that calreticulin serves as a cytosolic activator of integrin and a signal transducer between integrins and Ca2+ channels on the cell surface.