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Updated: Oct 27, 2025

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
Stimulation of Ca2+ -ATPase Transport Activity by a Small-Molecule Drug
Giacomo Sordi1,2, Andrea Goti1, Howard S Young3
1Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Italy.
Abstract:
The sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) hydrolyzes ATP to transport Ca2+ from the cytoplasm to the sarcoplasmic reticulum (SR) lumen, thereby inducing muscle relaxation. Dysfunctional SERCA has been related to various diseases. The identification of small-molecule drugs that can activate SERCA may offer a therapeutic approach to treat pathologies connected with SERCA malfunction. Herein, we propose a method to study the mechanism of interaction between SERCA and novel SERCA activators, i. e. CDN1163, using a solid supported membrane (SSM) biosensing approach. Native SR vesicles or reconstituted proteoliposomes containing SERCA were adsorbed on the SSM and activated by ATP concentration jumps. We observed that CDN1163 reversibly interacts with SERCA and enhances ATP-dependent Ca2+ translocation. The concentration dependence of the CDN1163 effect provided an EC50 =6.0±0.3 μM. CDN1163 was shown to act directly on SERCA and to exert its stimulatory effect under physiological Ca2+ concentrations. These results suggest that CDN1163 interaction with SERCA can promote a protein conformational state that favors Ca2+ release into the SR lumen.
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