Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development

39Citations
Citations of this article
65Readers
Mendeley users who have this article in their library.

Abstract

Atypical 7-transmembrane receptors, often called decoy receptors, act promiscuously as molecular sinks to regulate ligand bioavailability and consequently temper the signaling of canonical G protein-coupled receptor (GPCR) pathways. Loss of mammalian CXCR7, the most recently described decoy receptor, results in postnatal lethality due to aberrant cardiac development and myocyte hyperplasia. Here, we provide the molecular underpinning for this proliferative phenotype by demonstrating that the dosage and signaling of adrenomedullin (Adm, gene; AM, protein)-a mitogenic peptide hormone required for normal cardiovascular development-is tightly controlled by CXCR7. To this end, Cxcr7-/- mice exhibit gain-of-function cardiac and lymphatic vascular phenotypes that can be reversed upon genetic depletion of adrenomedullin ligand. In addition to identifying a biological ligand accountable for the phenotypes of Cxcr7-/- mice, these results reveal a previously underappreciated role for decoy receptors as molecular rheostats in controlling the timing and extent of GPCR-mediated cardiac and vascular development.

Cite

CITATION STYLE

APA

Klein, K. R., Karpinich, N. O., Espenschied, S. T., Willcockson, H. H., Dunworth, W. P., Hoopes, S. L., … Caron, K. M. (2014). Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development. Developmental Cell, 30(5), 528–540. https://doi.org/10.1016/j.devcel.2014.07.012

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free