Page 134 - ebook

[B. Cell Biology/Stem Cell] B-2

Calsequestrin 1 Is an Active Partner of Stromal Interaction

Molecule 2 in Skeletal Muscle

Seung Yeon Jeong¹,², Mi Ri Oh¹,², Jun Hee Choi¹,², Jin Seok Woo³, Eun Hui Lee¹,²*

¹Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea,

²Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul 06591,

Korea, ³Department of Physiology, David Geffen School of Medicine, UCLA, Los Angeles 10833, USA

Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca2+ in the SR. CASQ1 also regulates SOCE by
binding to stromal interaction molecule 1 (STIM1). Abnormal SOCE and/or abnormal expression or mutations in

CASQ1, STIM1, or STIM2 are associated with human skeletal, cardiac, or smooth muscle diseases. However, the
functional relevance of CASQ1 along with STIM2 has not been studied in any tissue, including skeletal muscle. First,

in the present study, it was found that CASQ1 is bound to STIM2 via its 92 N-terminal C1 region. Next, to examine
the functional relevance of the CASQ1-STIM2 interaction in skeletal muscle, the full-length wild-type CASQ1 or the

C1 region was expressed in mouse primary skeletal myotubes, and the myotubes were examined. The CASQ1-STIM2
interaction via the C1 region decreased SOCE, increased intracellular Ca2+ release for skeletal muscle contraction,

and changed intracellular Ca2+ distributions. Furthermore, the C1 region itself (which lacks Ca2+-buffering ability
but has STIM2-binding ability) decreased the expression of Ca2+-related proteins (TRPC 6 and calmodulin 1) and

induced mitochondrial shape abnormalities. Therefore, in skeletal muscle, CASQ1 plays active roles in Ca2+
movement and distribution by interacting with STIM2 as well as Ca2+ sensing and buffering.