Item type |
学術雑誌論文 / Journal Article(1) |
公開日 |
2022-12-01 |
タイトル |
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タイトル |
Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction |
言語 |
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言語 |
eng |
DOI |
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関連タイプ |
isVersionOf |
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関連識別子 |
https://doi.org/10.1073/pnas.1716649115 |
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関連名称 |
10.1073/pnas.1716649115 |
資源タイプ |
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資源 |
http://purl.org/coar/resource_type/c_6501 |
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タイプ |
journal article |
著者 |
Nakada, Tsutomu
Kashihara, Toshihide
Komatsu, Masatoshi
Kojima, Katsuhiko
Takeshita, Toshikazu
Yamada, Mitsuhiko
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信州大学研究者総覧へのリンク |
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氏名 |
中田, 勉 |
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URL |
https://soar-rd.shinshu-u.ac.jp/profile/ja.OVkhuNkh.html |
信州大学研究者総覧へのリンク |
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氏名 |
小嶋, 克彦 |
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URL |
https://soar-rd.shinshu-u.ac.jp/profile/ja.OCcFuakh.html |
信州大学研究者総覧へのリンク |
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氏名 |
小嶋, 克彦 |
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URL |
https://soar-rd.shinshu-u.ac.jp/profile/ja.OCcFuakh.html |
信州大学研究者総覧へのリンク |
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氏名 |
竹下, 敏一 |
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URL |
https://soar-rd.shinshu-u.ac.jp/profile/ja.uVLaOmSF.html |
信州大学研究者総覧へのリンク |
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氏名 |
山田, 充彦 |
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URL |
https://soar-rd.shinshu-u.ac.jp/profile/ja.jhSCupca.html |
出版者 |
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出版者 |
National Academy of Sciences |
引用 |
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内容記述 |
Proceedings of the National Academy of Sciences of the United States of America. 115(17) : 4507-4512(2018) |
書誌情報 |
Proceedings of the National Academy of Sciences of the United States of America.
巻 115,
号 17,
p. 4507-4512,
発行日 2018-04-24
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抄録 |
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内容記述 |
Close physical association of CaV1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors (RyRs) of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle. However, the molecular mechanism underlying the JM targeting of LTCCs is unexplored. Junctophilin 1 (JP1) and JP2 stabilize the JM by bridging the sarcolemmal and SR membranes. Here, we examined the roles of JPs in localization and function of LTCCs. Knockdown of JP1 or JP2 in cultured myotubes inhibited LTCC clustering at the JM and suppressed evoked Ca2+ transients without disrupting JM structure. Coimmunoprecipitation and GST pull-down assays demonstrated that JPs physically interacted with 12-aa residues in the proximal C terminus of the CaV1.1. A JP1 mutant lacking the C terminus including the transmembrane domain (JP1ΔCT) interacted with the sarcolemmal/T-tubule membrane but not the SR membrane. Expression of this mutant in adult mouse muscles in vivo exerted a dominant-negative effect on endogenous JPs, impairing LTCC-RyR coupling at triads without disrupting JM morphology, and substantially reducing Ca2+ transients without affecting SR Ca2+ content. Moreover, the contractile force of the JP1ΔCT-expressed muscle was dramatically reduced compared with the control. Taken together, JPs recruit LTCCs to the JM through physical interaction and ensure robust ECC at triads in skeletal muscle. |
資源タイプ(コンテンツの種類) |
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内容記述 |
Article |
ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1091-6490 |
PubMed |
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関連識別子 |
https://pubmed.ncbi.nlm.nih.gov/29632175/ |
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関連名称 |
29632175 |
権利 |
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権利情報 |
© Authors |
出版タイプ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |