Premium
T‐cadherin, an Adiponectin Receptor in the Cardiovascular System
Author(s) -
Denzel Martin Sebastian,
Scimia Maria Cecilia,
RuizLozano Pilar,
Shapiro Lawrence,
Ranscht Barbara
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.506.8
Subject(s) - adiponectin , adiponectin receptor 1 , medicine , ampk , endocrinology , cadherin , angiogenesis , receptor , chemistry , protein kinase a , biology , microbiology and biotechnology , phosphorylation , insulin resistance , insulin , biochemistry , cell
T‐cadherin, an atypical GPI‐anchored cadherin is expressed on endothelial and muscle cells. It binds Adiponectin, a fat‐derived cytokine with proangiogenic and cardioprotective properties. Adiponectin's serum concentration is inversely related to fat mass. Adiponectin activates AMP dependent protein kinase (AMPK) but the detailed mechanism remains elusive. We report that T‐cadherin is required for the effects of Adiponectin in the vasculature and the heart in vivo. Adiponectin binding to the surface of muscle fibers and blood vessels is abolished in mice genetically deficient for T‐cadherin. T‐cadherin‐dependent binding of Adiponectin was confirmed by siRNA‐mediated depletion of T‐cadherin in C2C12 myotubes and with endothelial cells overexpressing T‐cadherin. In the hind limb ischemia angiogenesis model both T‐cadherin‐ and Adiponectin‐deficient mice displayed reduced angiogenesis after hypoxia as compared to the wild type. Cardiac hypertrophy after pressure overload in mice lacking T‐cadherin or Adiponectin was enhanced compared to the wild type. AMPK phosphorylation in the hypertrophic hearts was significantly reduced in both T‐cadherin‐ and Adiponectin‐deficient mice. Our work suggests a mechanistic link between T‐cadherin's and Adiponectin's functions. We propose a model in which T‐cadherin mediates Adiponectin's protective effects as a receptor or coreceptor.