T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin

C Hug, J Wang, NS Ahmad, JS Bogan… - Proceedings of the …, 2004 - National Acad Sciences
C Hug, J Wang, NS Ahmad, JS Bogan, TS Tsao, HF Lodish
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
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 …
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.
National Acad Sciences