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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction

http://hdl.handle.net/10091/0002001245
http://hdl.handle.net/10091/0002001245
6b3a0520-b1c3-4567-a614-1c9782c4e3ea
名前 / ファイル ライセンス アクション
18K06870_2.pdf 18K06870_2.pdf
Item type 学術雑誌論文 / Journal Article(1)
公開日 2022-12-01
タイトル
言語 en
タイトル Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Nakada, Tsutomu

× Nakada, Tsutomu

en Nakada, Tsutomu

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Kashihara, Toshihide

× Kashihara, Toshihide

en Kashihara, Toshihide

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Komatsu, Masatoshi

× Komatsu, Masatoshi

en Komatsu, Masatoshi

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Kojima, Katsuhiko

× Kojima, Katsuhiko

en Kojima, Katsuhiko

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Takeshita, Toshikazu

× Takeshita, Toshikazu

en Takeshita, Toshikazu

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Yamada, Mitsuhiko

× Yamada, Mitsuhiko

en Yamada, Mitsuhiko

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信州大学研究者総覧へのリンク
氏名 中田, 勉
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
氏名 小嶋, 克彦
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
氏名 小嶋, 克彦
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
氏名 竹下, 敏一
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
氏名 山田, 充彦
URL https://soar-rd.shinshu-u.ac.jp/profile/ja.jhSCupca.html
出版者
出版者 National Academy of Sciences
引用
内容記述タイプ Other
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
抄録
内容記述タイプ Abstract
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)
内容記述タイプ Other
内容記述 Article
ISSN
収録物識別子タイプ EISSN
収録物識別子 1091-6490
PubMed
識別子タイプ PMID
関連識別子 https://pubmed.ncbi.nlm.nih.gov/29632175/
関連名称 29632175
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1073/pnas.1716649115
関連名称 10.1073/pnas.1716649115
権利
権利情報 © Authors
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
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