Calreticulin couples calcium release and calcium influx in integrin-mediated calcium signaling

The engagement of integrin alpha 7 in E63 skeletal muscle cells by laminin or anti-alpha 7 antibodies triggered transient elevations in the intracellular free Ca2+ concentration that resulted from both inositol triphosphate-evoked Ca-2+ release from intracellular stores and extracellular Ca2+ influx through voltage-gated, L-type Ca2+ channels. The extracellular domain of integrin alpha 7 was found to associate with both ectocalreticulin and dihydropyridine receptor on the cell surface. Calreticulin appears to also associate with cytoplasmic domain of integrin alpha 7 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.