Phosphorylation of heptahelical receptors is thought to regulate G protein signaling, receptor endocytosis, and non-canonical signaling via recruitment of β-arrestins. We investigated chemokine receptor functionality under phosphorylation-deficient and β-arrestin-deficient conditions by studying interneuron migration in the embryonic cortex. This process depends on CXCL12, CXCR4, G protein signaling and on the atypical CXCL12 receptor ACKR3. We found that phosphorylation was crucial, whereas β-arrestins were dispensable for ACKR3-mediated control of CXCL12 levels in vivo. Cortices of mice expressing phosphorylation-deficient ACKR3 exhibited a major interneuron migration defect, which was accompanied by excessive activation and loss of CXCR4. Cxcl12-overexpressing mice mimicked this phenotype. Excess CXCL12 caused lysosomal CXCR4 degradation, loss of CXCR4 responsiveness, and, ultimately, similar motility defects as Cxcl12 deficiency. By contrast, β-arrestin deficiency caused only a subtle migration defect mimicked by CXCR4 gain of function. These findings demonstrate that phosphorylation regulates atypical chemokine receptor function without β-arrestin involvement in chemokine sequestration and non-canonical signaling.
Pubmed ID: 30726732 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsThis monoclonal targets dsRed, mRFP, mCherry , mPlum, mRFPruby
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsThis monoclonal targets CD184
View all literature mentionsThis monoclonal targets Human CXCR7/RDC-1 MAb (Clone 11G8)
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis polyclonal targets Mouse Reelin
View all literature mentionsThis monoclonal targets Ctip2
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal targets Rat IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets alpha-Tubulin
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets Transferrin Receptor
View all literature mentionsThis polyclonal targets
View all literature mentionsThis monoclonal targets beta Arrestin 1 antibody [E274]
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis polyclonal targets Rabbit IgG H&L
View all literature mentionsThis monoclonal targets beta-Arrestin 2 (C16D9) Rabbit mAb
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG H&L
View all literature mentionsThis polyclonal targets IgY (IgG) (H+L)
View all literature mentions