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Identification and characterization of two ankyrin-B isoforms in mammalian heart.
Wu, Henry C; Yamankurt, Gokay; Luo, JiaLie; Subramaniam, Janani; Hashmi, Syed Shahrukh; Hu, Hongzhen; Cunha, Shane R.
Afiliación
  • Wu HC; Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSE R331, Houston, TX 77030, USA.
  • Yamankurt G; Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
  • Luo J; Department of Anesthesiology, the Center for the Study of Itch, Washington University Pain Center, Washington University School of Medicine in St Louis, St Louis, MO 63110, USA.
  • Subramaniam J; Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSE R331, Houston, TX 77030, USA.
  • Hashmi SS; Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
  • Hu H; Department of Anesthesiology, the Center for the Study of Itch, Washington University Pain Center, Washington University School of Medicine in St Louis, St Louis, MO 63110, USA.
  • Cunha SR; Department of Integrative Biology and Pharmacology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSE R331, Houston, TX 77030, USA shane.r.cunha@uth.tmc.edu.
Cardiovasc Res ; 107(4): 466-77, 2015 Sep 01.
Article en En | MEDLINE | ID: mdl-26109584
AIMS: Excitation-contraction coupling in cardiomyocytes requires the proper targeting and retention of membrane proteins to unique domains by adaptor proteins like ankyrin-B. While ankyrin-B has been shown to interact with a variety of membrane and structural proteins located at different subcellular domains in cardiomyocytes, what regulates the specificity of ankyrin-B for particular interacting proteins remains elusive. METHODS AND RESULTS: Here, we report the identification of two novel ankyrin-B isoforms AnkB-188 and AnkB-212 in human, rat, and mouse hearts. Novel cDNAs for both isoforms were isolated by long-range PCR of reverse-transcribed mRNA isolated from human ventricular tissue. The isoforms can be discriminated based on their function and subcellular distribution in cardiomyocytes. Heterologous overexpression of AnkB-188 increases sodium-calcium exchanger (NCX) membrane expression and current, while selective knockdown of AnkB-188 in cardiomyocytes reduces NCX expression and localization in addition to causing irregular contraction rhythms. Using an isoform-specific antibody, we demonstrate that the expression of AnkB-212 is restricted to striated muscles and is localized to the M-line of cardiomyocytes by interacting with obscurin. Selective knockdown of AnkB-212 significantly attenuates the expression of endogenous ankyrin-B at the M-line but does not disrupt NCX expression at transverse tubules in cardiomyocytes. CONCLUSION: The identification and characterization of two functionally distinct ankyrin-B isoforms in heart provide compelling evidence that alternative splicing of the ANK2 gene regulates the fidelity of ankyrin-B interactions with proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ancirinas / Miocardio Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Cardiovasc Res Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ancirinas / Miocardio Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Cardiovasc Res Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido