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Effective Attenuation of Adenosine A1R Signaling by Neurabin Requires Oligomerization of Neurabin.
Chen, Yunjia; Booth, Christopher; Wang, Hongxia; Wang, Raymond X; Terzi, Dimitra; Zachariou, Venetia; Jiao, Kai; Zhang, Jin; Wang, Qin.
Afiliação
  • Chen Y; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Booth C; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Wang H; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Wang RX; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Terzi D; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Zachariou V; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Jiao K; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Zhang J; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
  • Wang Q; Departments of Cell, Developmental, and Integrative Biology (Y.C., H.W., R.X.W., Q.W.) and Genetics (K.J.), University of Alabama, Birmingham, Alabama; Department of Pharmacology, University of California, San Diego, California (C.B., J.Z.); and Department of Neuroscience, Friedman Brain Institute,
Mol Pharmacol ; 92(6): 630-639, 2017 12.
Article em En | MEDLINE | ID: mdl-28954816
The adenosine A1 receptor (A1R) is a key mediator of the neuroprotective effect by endogenous adenosine. Yet targeting this receptor for neuroprotection is challenging due to its broad expression throughout the body. A mechanistic understanding of the regulation of A1R signaling is necessary for the future design of therapeutic agents that can selectively enhance A1R-mediated responses in the nervous system. In this study, we demonstrate that A1R activation leads to a sustained localization of regulator of G protein signaling 4 (RGS4) at the plasma membrane, a process that requires neurabin (a neural tissue-specific protein). A1R and RGS4 interact with the overlapping regions of neurabin. In addition, neurabin domains required for oligomerization are essential for formation of the A1R/neurabin/RGS4 ternary complex, as well as for stable localization of RGS4 at the plasma membrane and attenuation of A1R signaling. Thus, A1R and RGS4 each likely interact with one neurabin molecule in a neurabin homo-oligomer to form a ternary complex, representing a novel mode of regulation of G protein-coupled receptor signaling by scaffolding proteins. Our mechanistic analysis of neurabin-mediated regulation of A1R signaling in this study will be valuable for the future design of therapeutic agents that can selectively enhance A1R-mediated responses in the nervous system.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptor A1 de Adenosina / Proteínas dos Microfilamentos / Proteínas do Tecido Nervoso Limite: Animals / Humans Idioma: En Revista: Mol Pharmacol Ano de publicação: 2017 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptor A1 de Adenosina / Proteínas dos Microfilamentos / Proteínas do Tecido Nervoso Limite: Animals / Humans Idioma: En Revista: Mol Pharmacol Ano de publicação: 2017 Tipo de documento: Article