RRC ID 55986
Author Shintani Y, Hayata-Takano A, Moriguchi K, Nakazawa T, Ago Y, Kasai A, Seiriki K, Shintani N, Hashimoto H.
Title β-Arrestin1 and 2 differentially regulate PACAP-induced PAC1 receptor signaling and trafficking.
Journal PLoS One
Abstract A pituitary adenylate cyclase-activating polypeptide (PACAP)-specific receptor, PAC1R, is coupled with multiple signal transduction pathways including stimulation of adenylate cyclase, phospholipase C and extracellular-signal regulated kinase (ERK)1/2. PAC1R has been shown to exert its long-lasting and potent signals via β-arrestin1 and β-arrestin2. However, the precise roles of the two β-arrestin isoforms in PACAP-PAC1R signaling remain unclear. Here we examined the interaction between the two β-arrestin isoforms and PAC1R, β-arrestin-dependent PAC1R subcellular localization and ERK1/2 activation. Upon PACAP stimulation, although PAC1R similarly interacted with β-arrestin1 and β-arrestin2 in HEK293T cells, the complex of PAC1R and β-arrestin2 was translocated from the cell surface into cytosol, but that of β-arrestin1 remained in the cell surface regions in HeLa cells and mouse primary cultured neurons. Silencing of β-arrestin2 blocked PACAP-induced PAC1R internalization and ERK1/2 phosphorylation, but silencing of β-arrestin1 increased ERK1/2 phosphorylation. These results show that β-arrestin1 and β-arrestin2 exert differential actions on PAC1R internalization and PAC1R-dependent ERK1/2 activation, and suggest that the two β-arrestin isoforms may be involved in fine and precise tuning of the PAC1R signaling pathways.
Volume 13(5)
Pages e0196946
Published 2018-5-7
DOI 10.1371/journal.pone.0196946
PII PONE-D-18-03008
PMID 29734363
PMC PMC5937772
MeSH Adenylyl Cyclases / genetics Animals HEK293 Cells Humans Mice Mitogen-Activated Protein Kinase 3 / genetics Neurons / metabolism Pituitary Adenylate Cyclase-Activating Polypeptide / genetics Protein Isoforms / genetics* Protein Transport / genetics Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics* Signal Transduction / genetics Type C Phospholipases / genetics beta-Arrestin 1 / genetics* beta-Arrestin 2 / genetics*
IF 2.776
Times Cited 2
Human and Animal Cells HeLa(RCB0007)