دورية أكاديمية

Speg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads

التفاصيل البيبلوغرافية
العنوان: Speg interactions that regulate the stability of excitation-contraction coupling protein complexes in triads and dyads
المؤلفون: Chang Seok Lee, Sung Yun Jung, Rachel Sue Zhen Yee, Nadia H. Agha, Jin Hong, Ting Chang, Lyle W. Babcock, Jorie D. Fleischman, Benjamin Clayton, Amy D. Hanna, Christopher S. Ward, Denise Lanza, Ayrea E. Hurley, Pumin Zhang, Xander H. T. Wehrens, William R. Lagor, George G. Rodney, Susan L. Hamilton
المصدر: Communications Biology, Vol 6, Iss 1, Pp 1-19 (2023)
بيانات النشر: Nature Portfolio, 2023.
سنة النشر: 2023
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: Abstract Here we show that striated muscle preferentially expressed protein kinase α (Spegα) maintains cardiac function in hearts with Spegβ deficiency. Speg is required for stability of excitation-contraction coupling (ECC) complexes and interacts with esterase D (Esd), Cardiomyopathy-Associated Protein 5 (Cmya5), and Fibronectin Type III and SPRY Domain Containing 2 (Fsd2) in cardiac and skeletal muscle. Mice with a sequence encoding a V5/HA tag inserted into the first exon of the Speg gene (HA-Speg mice) display a >90% decrease in Spegβ but Spegα is expressed at ~50% of normal levels. Mice deficient in both Spegα and Speg β (Speg KO mice) develop a severe dilated cardiomyopathy and muscle weakness and atrophy, but HA-Speg mice display mild muscle weakness with no cardiac involvement. Spegα in HA-Speg mice suppresses Ca2+ leak, proteolytic cleavage of Jph2, and disruption of transverse tubules. Despite it’s low levels, HA-Spegβ immunoprecipitation identified Esd, Cmya5 and Fsd2 as Spegβ binding partners that localize to triads and dyads to stabilize ECC complexes. This study suggests that Spegα and Spegβ display functional redundancy, identifies Esd, Cmya5 and Fsd2 as components of both cardiac dyads and skeletal muscle triads and lays the groundwork for the identification of new therapeutic targets for centronuclear myopathy.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2399-3642
العلاقة: https://doaj.org/toc/2399-3642Test
DOI: 10.1038/s42003-023-05330-y
الوصول الحر: https://doaj.org/article/7a8ed53a9dd64509bc4efd890aaae296Test
رقم الانضمام: edsdoj.7a8ed53a9dd64509bc4efd890aaae296
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23993642
DOI:10.1038/s42003-023-05330-y