Cell Reports
Volume 3, Issue 5, 30 May 2013, Pages 1457-1464
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Report
Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116

https://doi.org/10.1016/j.celrep.2013.04.019Get rights and content
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Highlights

  • Gpr116 plays a critical nonredundant role in lung surfactant homeostasis

  • Gpr116 deletion results in surfactant accumulation in the alveolar space

  • Gpr116 regulates surfactant composition and uptake by alveolar type II cells

  • Modulation of GPR116 activity could aid in treatment of lung surfactant disorders

Summary

GPR116 is an orphan seven-pass transmembrane receptor whose function has been unclear. Global disruption of the Gpr116 gene in mice revealed an unexpected, critical role for this receptor in lung surfactant homeostasis, resulting in progressive accumulation of surfactant lipids and proteins in the alveolar space, labored breathing, and a reduced lifespan. GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. Aberrant packaging of surfactant proteins with lipids in the Gpr116 mutant mice resulted in compromised surfactant structure, function, uptake, and processing. Thus, GPR116 plays an indispensable role in lung surfactant homeostasis with important ramifications for the understanding and treatment of lung surfactant disorders.

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