A novel sorting sequence in the beta2-adrenergic receptor switches recycling from default to the Hrs-dependent mechanism.
Plasma membrane recycling of G protein-coupled receptors can occur by at least two distinct mechanisms as follows: a "default" mechanism that occurs nonselectively, and a specifically sorted mechanism that requires the endosome-associated protein Hrs. In this study we have defined a sequence in the beta2-adrenergic receptor cytoplasmic tail that confers Hrs dependence on receptor recycling. This sequence resembles acidic dileucine class motifs found in other membrane proteins but is structurally and functionally distinct from previously identified sorting sequences. Mutation of the novel sorting sequence rendered plasma membrane recycling independent of Hrs and independent of a distal PDZ ligand required for Hrs-dependent recycling. We propose that the novel sorting sequence functions to "switch" endocytic trafficking between mechanistically distinct recycling modes, thereby explaining failure of the wild type beta2-adrenergic receptor to recycle efficiently by default.
Hanyaloglu
Aylin C
AC
Department of Psychiatry, University of California, San Francisco, California 94158, USA.
von Zastrow
Mark
M
D000595:Amino Acid Sequence; D056827:Endosomal Sorting Complexes Required for Transport; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D056827:Endosomal Sorting Complexes Required for Transport; D010446:Peptide Fragments; D010750:Phosphoproteins; D018343:Receptors, Adrenergic, beta-2; D011994:Recombinant Proteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate