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

Published

Journal Article

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.

Full Text

Cited Authors

  • Klein, KR; Karpinich, NO; Espenschied, ST; Willcockson, HH; Dunworth, WP; Hoopes, SL; Kushner, EJ; Bautch, VL; Caron, KM

Published Date

  • September 2014

Published In

Volume / Issue

  • 30 / 5

Start / End Page

  • 528 - 540

PubMed ID

  • 25203207

Pubmed Central ID

  • 25203207

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

International Standard Serial Number (ISSN)

  • 1534-5807

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2014.07.012

Language

  • eng