© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 tripleKOmice, calcium transients induced by tetanic stimulation rely on calcium entry via La 3+ - and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45- CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca 2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca 2+ concentrations similar to those present in the SR lumen after depolarizationinduced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs.
Mosca, B., Eckhardt, J., Bergamelli, L., Treves, S., Bongianino, R., De Negri, M., … Zorzato, F. (2016). Role of the JP45-calsequestrin complex on calcium entry in slow twitch skeletal muscles. Journal of Biological Chemistry, 291(28), 14555–14565. https://doi.org/10.1074/jbc.M115.709071