β-arrestin control of late endosomal sorting facilitates decoy receptor function and chemokine gradient formation.
A crucial regulator of Cxcl12 is the decoy receptor Cxcr7, which controls the level of the chemokine in the tissue. The molecular mechanisms that enable Cxcr7 to function as an efficient molecular sink are not known. Using zebrafish primordial germ cells as a model, we identify a novel role for β-arrestins in controlling the intracellular trafficking of Cxcr7. β-arrestins facilitate the recycling of Cxcr7 from late endosomal compartments back to the plasma membrane, whereas the internalized ligand undergoes lysosomal degradation. β-arrestins thus function in regulating chemokine gradient formation, allowing responding cells to discriminate between alternative migration targets in vivo.
Institute of Cell Biology, ZMBE, University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany.
Harsha
H
Mahabaleshwar
Katsiaryna
K
Tarbashevich
Matthias
M
Nowak
Michael
M
Brand
Erez
E
Raz
D000818:Animals; D030801:Animals, Genetically Modified; D019390:Arrestins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins
D019390:Arrestins; C519524:CXCR7 protein, zebrafish; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D029961:Zebrafish Proteins; D000071557:beta-Arrestins