TY - JOUR
T1 - Substance P-induced trafficking of β-arrestins
T2 - The role of β- arrestins in endocytosis of the neurokinin-1 receptor
AU - McConalogue, Karen
AU - Déry, Olivier
AU - Lovett, Michelle
AU - Wong, Helen
AU - Walsh, John H.
AU - Grady, Eileen F.
AU - Bunnett, Nigel W.
PY - 1999/6/4
Y1 - 1999/6/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0039702902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0039702902&partnerID=8YFLogxK
U2 - 10.1074/jbc.274.23.16257
DO - 10.1074/jbc.274.23.16257
M3 - Article
C2 - 10347182
AN - SCOPUS:0039702902
SN - 0021-9258
VL - 274
SP - 16257
EP - 16268
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 23
ER -