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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin.
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T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin.

机译:T-钙粘蛋白是Acrp30 /脂联素的六聚体和高分子量形式的受体。

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摘要

Acrp30/adiponectin is reduced in the serum of obese and diabetic individuals, and the genetic locus of adiponectin is linked to the metabolic syndrome. Recombinant adiponectin, administered to diet-induced obese mice, induced weight loss and improved insulin sensitivity. In muscle and liver, adiponectin stimulates AMP-activated protein kinase activation and fatty acid oxidation. To expression-clone molecules capable of binding adiponectin, we transduced a C2C12 myoblast cDNA retroviral expression library into Ba/F3 cells and panned infected cells on recombinant adiponectin linked to magnetic beads. We identified T-cadherin as a receptor for the hexameric and high-molecular-weight species of adiponectin but not for the trimeric or globular species. Only eukaryotically expressed adiponectin bound to T-cadherin, implying that posttranslational modifications of adiponectin are critical for binding. An adiponectin mutant lacking a conserved N-terminal cysteine residue required for formation of hexamer and high-molecular-weight species did not bind T-cadherin in coimmunoprecipitation studies. Although lacking known cellular functions, T-cadherin is expressed in endothelial and smooth muscle cells, where it is positioned to interact with adiponectin. Because T-cadherin is a glycosylphosphatidylinositol-anchored extracellular protein, it may act as a coreceptor for an as-yet-unidentified signaling receptor through which adiponectin transmits metabolic signals.
机译:肥胖和糖尿病患者血清中的Acrp30 /脂联素降低,脂联素的遗传基因位点与代谢综合征相关。对饮食诱导的肥胖小鼠施用重组脂联素,可减轻体重并改善胰岛素敏感性。在肌肉和肝脏中,脂连蛋白刺激AMP激活的蛋白激酶激活和脂肪酸氧化。为了表达能够结合脂联素的克隆分子,我们将C2C12成肌细胞cDNA逆转录病毒表达文库转导到Ba / F3细胞中,并在与磁珠相连的重组脂联素上淘选感染的细胞。我们确定T-钙粘着蛋白是脂联素的六聚体和高分子量物种的受体,而不是三聚体或球状物种的受体。只有真核表达的脂联素与T-钙粘着蛋白结合,这暗示脂联素的翻译后修饰对于结合至关重要。在共免疫沉淀研究中,缺乏形成六聚体和高分子量物种所需的保守的N端半胱氨酸残基的脂联素突变体不结合T-钙粘着蛋白。尽管缺乏已知的细胞功能,但T-钙粘着蛋白在内皮和平滑肌细胞中表达,并与脂联素相互作用。由于T-钙粘着蛋白是糖基磷脂酰肌醇固定的细胞外蛋白,它可能作为脂联素通过其传递代谢信号的尚未确定的信号受体的共受体。

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