Substance P-induced trafficking of β-arrestins: The role of β- arrestins in endocytosis of the neurokinin-1 receptor

Karen McConalogue, Olivier Déry, Michelle Lovett, Helen Wong, John H. Walsh, Eileen F. Grady, Nigel W. Bunnett

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Agonist-induced redistribution of G-protein-coupled receptors (GPCRs) and β-arrestins determines the subsequent cellular responsiveness to agonists and is important for signal transduction. We examined substance P (SP)-induced trafficking of β-arrestin1 and the neurokinin-1 receptor (NK1R) in KNRK cells in real time using green fluorescent protein. Green fluorescent protein did not alter function or localization of the NK1R or β-arrestin1. SP induced (a) striking and rapid (<1 min) translocation of β-arrestin1 from the cytosol to the plasma membrane, which preceded NK1R endocytosis; (b) redistribution of the NK1R and β-arrestin1 into the same endosomes containing SP and the transferrin receptor (2-10 min); (c) prolonged colocalization of the NK1R and β-arrestin1 in endosomes (>60 min); (d) gradual resumption of the steady state distribution of the NK1R at the plasma membrane and β-arrestin1 in the cytosol (4-6 h). SP stimulated a similar redistribution of immunoreactive β-arrestin1 and β-arrestin2. In contrast, SP did not affect Gα(q/11) distribution, which remained at the plasma membrane. Expression of the dominant negative β-arrestin319-418 inhibited SP-induced endocytosis of the NK1R. Thus, SP induces rapid translocation of β-arrestins to the plasma membrane, where they participate in NK1R endocytosis. β-Arrestins colocalize with the NK1R in endosomes until the NK1R recycles and β-arrestins return to the cytosol.

Original languageEnglish (US)
Pages (from-to)16257-16268
Number of pages12
JournalJournal of Biological Chemistry
Issue number23
StatePublished - Jun 4 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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