Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116

Mi Young Yang, Mary Beth Hilton, Steven Seaman, Diana C. Haines, Kunio Nagashima, Christina M. Burks, Lino Tessarollo, Pavlina T. Ivanova, H. Alex Brown, Todd M. Umstead, Joanna Floros, Zissis C. Chroneos, Brad St.Croix

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1457-1464
Number of pages8
JournalCell Reports
Volume3
Issue number5
DOIs
StatePublished - May 30 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yang, M. Y., Hilton, M. B., Seaman, S., Haines, D. C., Nagashima, K., Burks, C. M., Tessarollo, L., Ivanova, P. T., Brown, H. A., Umstead, T. M., Floros, J., Chroneos, Z. C., & St.Croix, B. (2013). Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116. Cell Reports, 3(5), 1457-1464. https://doi.org/10.1016/j.celrep.2013.04.019