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

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.
Mesh Terms:
Adiponectin, Adipose Tissue, Animals, CHO Cells, Cadherins, Cricetinae, Flow Cytometry, Gene Expression, Humans, Intercellular Signaling Peptides and Proteins, Kidney, Ligands, Magnetics, Mice, Molecular Weight, Myoblasts, Plasmids, Protein Binding, Proteins, Signal Transduction
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 13, 2004
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