title: Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway.
abstract: In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 (AdipoR1) and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K(+) trapped AdipoR1 at the plasma membrane, and K(+) depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K(+) and overexpression of Eps15 mutants enhance adiponectin-stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might downregulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5-dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai, China.
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Ding
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002451:Cell Compartmentation; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D054419:Receptors, Adiponectin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D002966:Clathrin; D054419:Receptors, Adiponectin; D014168:Transferrin; D055372:AMP-Activated Protein Kinases; D020696:rab5 GTP-Binding Proteins