Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle

Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca<sup>2+</sup> in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca<sup>2+</sup> entry (SOCE) by binding to stromal interaction molecule 1 (STIM1). Abnormal SOCE and/or abnormal expression or...

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Autores principales:	Seung Yeon Jeong, Mi Ri Oh, Jun Hee Choi, Jin Seok Woo, Eun Hui Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CASQ1 STIM2 SOCE skeletal muscle Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/799be74975654b0fba21f807066422ea
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spelling	oai:doaj.org-article:799be74975654b0fba21f807066422ea2021-11-25T17:07:35ZCalsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle10.3390/cells101128212073-4409https://doaj.org/article/799be74975654b0fba21f807066422ea2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2821https://doaj.org/toc/2073-4409Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca<sup>2+</sup> in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca<sup>2+</sup> entry (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 by biochemical approaches that CASQ1 is bound to STIM2 via its 92 N-terminal amino acids (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 using single-myotube Ca<sup>2+</sup> imaging experiments and transmission electron microscopy observations. The CASQ1-STIM2 interaction via the C1 region decreased SOCE, increased intracellular Ca<sup>2+</sup> release for skeletal muscle contraction, and changed intracellular Ca<sup>2+</sup> distributions (high Ca<sup>2+</sup> in the SR and low Ca<sup>2+</sup> in the cytosol were observed). Furthermore, the C1 region itself (which lacks Ca<sup>2+</sup>-buffering ability but has STIM2-binding ability) decreased the expression of Ca<sup>2+</sup>-related proteins (canonical-type transient receptor potential cation channel type 6 and calmodulin 1) and induced mitochondrial shape abnormalities. Therefore, in skeletal muscle, CASQ1 plays active roles in Ca<sup>2+</sup> movement and distribution by interacting with STIM2 as well as Ca<sup>2+</sup> sensing and buffering.Seung Yeon JeongMi Ri OhJun Hee ChoiJin Seok WooEun Hui LeeMDPI AGarticleCASQ1STIM2SOCEskeletal muscleBiology (General)QH301-705.5ENCells, Vol 10, Iss 2821, p 2821 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CASQ1 STIM2 SOCE skeletal muscle Biology (General) QH301-705.5
spellingShingle	CASQ1 STIM2 SOCE skeletal muscle Biology (General) QH301-705.5 Seung Yeon Jeong Mi Ri Oh Jun Hee Choi Jin Seok Woo Eun Hui Lee Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
description	Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca<sup>2+</sup> in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca<sup>2+</sup> entry (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 by biochemical approaches that CASQ1 is bound to STIM2 via its 92 N-terminal amino acids (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 using single-myotube Ca<sup>2+</sup> imaging experiments and transmission electron microscopy observations. The CASQ1-STIM2 interaction via the C1 region decreased SOCE, increased intracellular Ca<sup>2+</sup> release for skeletal muscle contraction, and changed intracellular Ca<sup>2+</sup> distributions (high Ca<sup>2+</sup> in the SR and low Ca<sup>2+</sup> in the cytosol were observed). Furthermore, the C1 region itself (which lacks Ca<sup>2+</sup>-buffering ability but has STIM2-binding ability) decreased the expression of Ca<sup>2+</sup>-related proteins (canonical-type transient receptor potential cation channel type 6 and calmodulin 1) and induced mitochondrial shape abnormalities. Therefore, in skeletal muscle, CASQ1 plays active roles in Ca<sup>2+</sup> movement and distribution by interacting with STIM2 as well as Ca<sup>2+</sup> sensing and buffering.
format	article
author	Seung Yeon Jeong Mi Ri Oh Jun Hee Choi Jin Seok Woo Eun Hui Lee
author_facet	Seung Yeon Jeong Mi Ri Oh Jun Hee Choi Jin Seok Woo Eun Hui Lee
author_sort	Seung Yeon Jeong
title	Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
title_short	Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
title_full	Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
title_fullStr	Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
title_full_unstemmed	Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle
title_sort	calsequestrin 1 is an active partner of stromal interaction molecule 2 in skeletal muscle
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/799be74975654b0fba21f807066422ea
work_keys_str_mv	AT seungyeonjeong calsequestrin1isanactivepartnerofstromalinteractionmolecule2inskeletalmuscle AT mirioh calsequestrin1isanactivepartnerofstromalinteractionmolecule2inskeletalmuscle AT junheechoi calsequestrin1isanactivepartnerofstromalinteractionmolecule2inskeletalmuscle AT jinseokwoo calsequestrin1isanactivepartnerofstromalinteractionmolecule2inskeletalmuscle AT eunhuilee calsequestrin1isanactivepartnerofstromalinteractionmolecule2inskeletalmuscle
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Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle

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