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.
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