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.

journal_name

Neuron

journal_title

Neuron

authors

Sánchez-Alcañiz JA,Haege S,Mueller W,Pla R,Mackay F,Schulz S,López-Bendito G,Stumm R,Marín O

doi

10.1016/j.neuron.2010.12.006

subject

Has Abstract

pub_date

2011-01-13 00:00:00

pages

77-90

issue

1

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(10)00991-8

journal_volume

69

pub_type

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