Rab11a and its binding partners regulate the recycling of the ß1-adrenergic receptor

Cell Signal. 2011 Jan;23(1):46-57. doi: 10.1016/j.cellsig.2010.07.020. Epub 2010 Aug 18.


ß1-adrenergic receptors (ß1-AR) are internalized in response to agonists and then recycle back for another round of signaling. The serine 312 to alanine mutant of the ß1-AR (S312A) is internalized but does not recycle. We determined that WT ß1-AR and S312A were internalized initially to an early sorting compartment because they colocalized by >70% with the early endosomal markers rab5a and early endosomal antigen-1 (EEA1). Subsequently, the WT ß1-AR trafficked via rab4a-expressing sorting endosomes to recycling endosomes. In recycling endosomes WT ß1-AR were colocalized by >70% with the rab11 GTPase. S312A did not colocalize with either rab4a or rab11, instead they exited from early endosomes to late endosomes/lysosomes in which they were degraded. Rab11a played a prominent role in recycling of the WT ß1-AR because dominant negative rab11a inhibited, while constitutively active rab11a accelerated the recycling of the ß1-AR. Next, we determined the effect of each of the rab11-interacting proteins on trafficking of the WT ß1-AR. The recycling of the ß1-AR was markedly inhibited when myosin Vb, FIP2, FIP3 and rabphillin were knocked down. These data indicate that rab11a and a select group of its binding partners play a prominent role in recycling of the human ß1-AR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Amino Acid Substitution
  • Cell Line
  • Endosomes / metabolism
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism
  • Isoproterenol / pharmacology
  • Lysosomes / metabolism
  • Mutagenesis, Site-Directed
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Myosin Type V / genetics
  • Myosin Type V / metabolism
  • RNA Interference
  • Receptors, Adrenergic, beta-1 / chemistry
  • Receptors, Adrenergic, beta-1 / genetics
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Vesicular Transport Proteins / metabolism
  • rab GTP-Binding Proteins / metabolism*
  • rab GTP-Binding Proteins / physiology
  • rab4 GTP-Binding Proteins / metabolism
  • rab4 GTP-Binding Proteins / physiology


  • Adrenergic beta-Agonists
  • IKBKG protein, human
  • MYO5B protein, human
  • Receptors, Adrenergic, beta-1
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • I-kappa B Kinase
  • Myosin Type V
  • rab11 protein
  • Myosin Heavy Chains
  • rab GTP-Binding Proteins
  • rab4 GTP-Binding Proteins
  • Isoproterenol