Stromal interaction molecule 1 (STIM1) regulates sarcoplasmic/endoplasmic reticulum Ca^sup 2+^-ATPase 1a (SERCA1a) in skeletal muscle

• Published in: Pflügers Archiv 2014-05, Vol.466 (5), p.987
• Main Authors: Lee, Keon Jin, Hyun, Changdo, Woo, Jin Seok, Park, Chang Sik, Kim, Do Han, Lee, Eun Hui
• Format: Article
• Language: English
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-013-1361-6

Stromal interaction molecule 1 (STIM1) mediates Ca^sup 2+^ movements from the extracellular space to the cytosol through a store-operated Ca^sup 2+^ entry (SOCE) mechanism in various cells including skeletal muscle cells. In the present study, to reveal the unidentified functional role of the STIM1 C terminus from 449 to 671 amino acids in skeletal muscle, binding assays and quadrupole time-of-flight mass spectrometry were used to identify proteins binding in this region along with proteins that mediate skeletal muscle contraction and relaxation. STIM1 binds to sarcoplasmic/endoplasmic reticulum Ca^sup 2+^-ATPase 1a (SERCA1a) via this region (called STIM1-SBR). The binding was confirmed in endogenous full-length STIM1 in rabbit skeletal muscle and mouse primary skeletal myotubes via co-immunoprecipitation assay and immunocytochemistry. STIM1 knockdown in mouse primary skeletal myotubes decreased Ca^sup 2+^ uptake from the cytosol to the sarcoplasmic reticulum (SR) through SERCA1a only at micromolar cytosolic Ca^sup 2+^ concentrations, suggesting that STIM1 could be required for the full activity of SERCA1a possibly during the relaxation of skeletal muscle. Various Ca^sup 2+^ imaging experiments using myotubes expressing STIM1-SBR suggest that STIM1 is involved in intracellular Ca^sup 2+^ distributions between the SR and the cytosol via regulating SERCA1a activity without affecting SOCE. Therefore, in skeletal muscle, STIM1 could play an important role in regulating Ca^sup 2+^ movements between the SR and the cytosol.[PUBLICATION ABSTRACT]