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Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1.

Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Research Abstract Details 

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  • Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Abstract Text:

    wusheng yanWusheng Yan,lynn spruceLynn Spruce,michael m rosenblattMichael M Rosenblatt,thomas r kleymanThomas R Kleyman,ronald c rubensteinRonald C Rubenstein,

    The A663T polymorphism of the alpha-subunit of the human epithelial sodium channel (hENaC) increases the functional and surface expression of alphabetagamma-hENaC in Xenopus laevis oocytes, and the context of this residue in the COOH terminus of alpha-hENaC is important for this effect. Query of a phosphoprotein database suggested that the alpha-T663 residue of hENaC might be a substrate for phosphorylation by casein kinase 1 (CK1). We tested the hypotheses that phosphorylation of alpha-T663-hENaC by CK1 would regulate the increased functional and surface expression of alpha-T663-hENaC vs. alpha-A663-hENaC in oocytes. General inhibition of CK1 with IC261 decreased the functional and surface expression of alpha-T663-hENaC, but not alpha-A663-hENaC. This decrease in alpha-T663-hENaC functional expression resulted from reduced delivery of alpha-T663-hENaC to the oocyte membrane. IC261 also inhibited the functional expression of alpha-T692-mENaC and a chimeric m(1-678)/h(650-669)alpha-T663, mbetagamma ENaC, but not alpha-A692-mENaC or m(1-678)/h(650-669)alpha-A663, mbetagamma ENaC. These data suggest that additional residues outside of the alpha-hENaC COOH terminus are important for modulation of alpha-T663-hENaC trafficking by CK1. Overexpression of CK1alpha did not alter functional expression of alpha-T663-hENaC. In contrast, modest overexpression of CK1delta enhanced, whereas higher levels of CK1delta overexpression inhibited alpha-T663-hENaC functional expression. CK1 did not phosphorylate the COOH terminus of either alpha-T663-hENaC or alpha-A663-hENaC in vitro. These data suggest that CK1, and perhaps specifically CK1delta, regulates the intracellular trafficking of the alpha-A663T functional polymorphism of hENaC indirectly by altering the rate of alpha-T663-hENaC biosynthesis and/or delivery to the plasma membrane.

    Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Publishing Authors By Initials

    w yanW Yan,l spruceL Spruce,mm rosenblattMM Rosenblatt,tr kleymanTR Kleyman,rc rubensteinRC Rubenstein,

    For similar animals: chordata: vertebrates: amphibia: anura: pipidae: xenopus: xenopus laevis research abstracts see: animals: chordata: vertebrates: amphibia: anura: pipidae: xenopus: xenopus laevis research

    PUBMED ID PMID:

    MEDLINE DATE:

    Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: American journal of physiology. Renal physiology

    VOLUME: 293

    Page Numbers: F868-76

    Journal Abbreviation: Am. J. Physiol. Renal Physiol.

    ISSN: 0363-6127

    DAY: 27

    MONTH: 06

    YEAR: 2007

    Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 100901990

    Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Keywords Mesh Terms:

    KEYWORDS: Xenopus laevis

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Information

    Substance Name: Casein Kinase I

    Registry Number: EC 2.7.1.37

    Grant and Affiliation Information for Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1.

    AFFILIATION: Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, PA, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDDK

    GRANT: DK-58046

    ACRONYM: DK

    MEDLINETA: Am J Physiol Renal Physiol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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    Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1 Related Publications

     

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