title: Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116.
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.
authors.affiliation: Tumor Angiogenesis Section, Mouse Cancer Genetics Program (MCGP), Center for Cancer Research (CCR), National Cancer Institute (NCI), Frederick, MD 21702, USA.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Yang
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hilton
authors.forename: Steven
authors.initials: S
authors.lastname: Seaman
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Christina M
authors.initials: CM
authors.lastname: Burks
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Pavlina T
authors.initials: PT
authors.lastname: Ivanova
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
authors.forename: Zissis C
authors.initials: ZC
authors.lastname: Chroneos
authors.forename: Brad
authors.initials: B
authors.lastname: St Croix
mesh_terms: D000818:Animals; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C577038:Gpr116 protein, mouse; D011663:Pulmonary Surfactants; D043562:Receptors, G-Protein-Coupled