Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function.

To determine how regulation of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) affects the Ca content of the endoplasmic reticulum (ER), we developed a ratiometric ER-localized Ca indicator to rapidly quantify Ca stores and assess SERCA function in live cells. This assay enables screening of membrane micropeptides and small molecules that modulate SERCA and Na/K-ATPase activity and may facilitate development of therapies that target cellular Ca handling. Of the micropeptides tested, phospholamban (PLB) had the greatest degree of inhibition of SERCA, as measured by a decrease in ER Ca content compared to control.