The fate of the internalized apelin receptor is determined by different isoforms of apelin mediating differential interaction with beta-arrestin

Biochem Biophys Res Commun. 2010 Apr 30;395(2):185-9. doi: 10.1016/j.bbrc.2010.03.151. Epub 2010 Mar 28.


Internalization of the apelin receptor by apelin-13 is characterized by dissociation from beta-arrestins and rapid recycling to the cell surface. Paradoxically, the apelin receptor internalized by apelin-36 was sequestered intracellularly. The specific pathways involved in apelin receptor trafficking were resolved using beta-arrestin1 and constitutively active and dominant negative Rab proteins following activation by apelin-13 or apelin-36. beta-Arrestin1 dissociated from the apelin-13-internalized receptor while the apelin-36-internalized receptor was trafficked with beta-arrestin1 to intracellular compartments. The apelin-13-internalized receptor was rapidly recycled to the cell surface through a Rab4-dependent mechanism while Rab7 targeted the receptor to lysosomes. The internalized receptor co-expressed with dominant negative Rab4 were trafficked to lysosomes. These observations revealed a novel ligand-dependent targeting of the apelin receptor to beta-arrestin-associated and -dissociated trafficking pathways and a role for different Rab proteins to direct these pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apelin
  • Apelin Receptors
  • Arrestins / metabolism*
  • Cell Line
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Protein Isoforms / metabolism
  • Protein Transport
  • Receptors, G-Protein-Coupled / metabolism*
  • beta-Arrestins
  • rab GTP-Binding Proteins / metabolism
  • rab4 GTP-Binding Proteins / metabolism


  • APLN protein, human
  • APLNR protein, human
  • Apelin
  • Apelin Receptors
  • Arrestins
  • Intercellular Signaling Peptides and Proteins
  • Protein Isoforms
  • Receptors, G-Protein-Coupled
  • apelin-13 peptide
  • beta-Arrestins
  • rab7 protein
  • rab GTP-Binding Proteins
  • rab4 GTP-Binding Proteins