Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway

Cell Res. 2009 Mar;19(3):317-27. doi: 10.1038/cr.2008.299.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adiponectin / metabolism
  • Animals
  • Cell Compartmentation
  • Clathrin / metabolism*
  • Endocytosis*
  • HeLa Cells
  • Humans
  • Mice
  • Phosphorylation
  • Receptors, Adiponectin / metabolism*
  • Transferrin / metabolism
  • rab5 GTP-Binding Proteins / metabolism*

Substances

  • ADIPOR1 protein, human
  • Adiponectin
  • Clathrin
  • Receptors, Adiponectin
  • Transferrin
  • AMP-Activated Protein Kinases
  • rab5 GTP-Binding Proteins