title: Cxcr7 controls neuronal migration by regulating chemokine responsiveness.
abstract: The chemokine Cxcl12 binds Cxcr4 and Cxcr7 receptors to control cell migration in multiple biological contexts, including brain development, leukocyte trafficking, and tumorigenesis. Both receptors are expressed in the CNS, but how they cooperate during migration has not been elucidated. Here, we used the migration of cortical interneurons as a model to study this process. We found that Cxcr4 and Cxcr7 are coexpressed in migrating interneurons, and that Cxcr7 is essential for chemokine signaling. Intriguingly, this process does not exclusively involve Cxcr7, but most critically the modulation of Cxcr4 function. Thus, Cxcr7 is necessary to regulate Cxcr4 protein levels, thereby adapting chemokine responsiveness in migrating cells. This demonstrates that a chemokine receptor modulates the function of another chemokine receptor by controlling the amount of protein that is made available for signaling at the cell surface.
authors.affiliation: Instituto de Neurociencias, Consejo Superior Universidad Miguel Hernández, Sant Joan d'Alacant 03550, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Sánchez-Alcañiz
authors.forename: Sammy
authors.initials: S
authors.lastname: Haege
authors.forename: Wiebke
authors.initials: W
authors.lastname: Mueller
authors.forename: Ramón
authors.initials: R
authors.lastname: Pla
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Guillermina
authors.initials: G
authors.lastname: López-Bendito
authors.forename: Ralf
authors.initials: R
authors.lastname: Stumm
authors.forename: Oscar
authors.initials: O
authors.lastname: Marín
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development; D054377:Chemokine CXCL12 / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR; D019718:Receptors, CXCR4