Developmental Vascular Remodeling Defects and Postnatal Kidney Failure in Mice Lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4)

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Aug 15

PMID 28806758

Citations 23

Authors

Shun Lu

Shuya Liu

Astrid Wietelmann

Baktybek Kojonazarov

Ann Atzberger

Cong Tang

Ralph Theo Schermuly

Hermann-Josef Grone

Stefan Offermanns

Affiliations

Soon will be listed here.

Abstract

GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced. Loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells did not recapitulate any of the phenotypes observed in GPR116-ELTD1 double deficient mice, indicating that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.

Citing Articles

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References

Nechiporuk T, Urness L, Keating M . ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily. J Biol Chem. 2000; 276(6):4150-7. DOI: 10.1074/jbc.M004814200. View

Lin H, Stacey M, Yona S, Chang G . GPS proteolytic cleavage of adhesion-GPCRs. Adv Exp Med Biol. 2011; 706:49-58. DOI: 10.1007/978-1-4419-7913-1_4. View

Noris M, Mescia F, Remuzzi G . STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012; 8(11):622-33. DOI: 10.1038/nrneph.2012.195. View

Liebscher I, Schon J, Petersen S, Fischer L, Auerbach N, Demberg L . A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep. 2014; 9(6):2018-26. PMC: 4277498. DOI: 10.1016/j.celrep.2014.11.036. View

Kavanagh D, Goodship T, Richards A . Atypical hemolytic uremic syndrome. Semin Nephrol. 2013; 33(6):508-30. PMC: 3863953. DOI: 10.1016/j.semnephrol.2013.08.003. View

Bridges J, Ludwig M, Mueller M, Kinzel B, Sato A, Xu Y . Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. Am J Respir Cell Mol Biol. 2013; 49(3):348-57. PMC: 3824053. DOI: 10.1165/rcmb.2012-0439OC. View

High F, Zhang M, Proweller A, Tu L, Parmacek M, Pear W . An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007; 117(2):353-63. PMC: 1783803. DOI: 10.1172/JCI30070. View

Favara D, Banham A, Harris A . A review of ELTD1, a pro-angiogenic adhesion GPCR. Biochem Soc Trans. 2014; 42(6):1658-64. DOI: 10.1042/BST20140216. View

Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T . Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest. 1995; 96(1):293-300. PMC: 185200. DOI: 10.1172/JCI118033. View

10.

Gittenberger-de Groot A, Bartelings M, Poelmann R, Haak M, Jongbloed M . Embryology of the heart and its impact on understanding fetal and neonatal heart disease. Semin Fetal Neonatal Med. 2013; 18(5):237-44. DOI: 10.1016/j.siny.2013.04.008. View

11.

Takase H, Matsumoto K, Yamadera R, Kubota Y, Otsu A, Suzuki R . Genome-wide identification of endothelial cell-enriched genes in the mouse embryo. Blood. 2012; 120(4):914-23. DOI: 10.1182/blood-2011-12-398156. View

12.

Fujita M, Sakabe M, Ioka T, Watanabe Y, Kinugasa-Katayama Y, Tsuchihashi T . Pharyngeal arch artery defects and lethal malformations of the aortic arch and its branches in mice deficient for the Hrt1/Hey1 transcription factor. Mech Dev. 2015; 139:65-73. DOI: 10.1016/j.mod.2015.11.002. View

13.

Paavola K, Stephenson J, Ritter S, Alter S, Hall R . The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity. J Biol Chem. 2011; 286(33):28914-28921. PMC: 3190698. DOI: 10.1074/jbc.M111.247973. View

14.

Arac D, Boucard A, Bolliger M, Nguyen J, Soltis S, Sudhof T . A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J. 2012; 31(6):1364-78. PMC: 3321182. DOI: 10.1038/emboj.2012.26. View

15.

Makki N, Capecchi M . Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum Mol Genet. 2011; 21(1):26-31. PMC: 3235008. DOI: 10.1093/hmg/ddr434. View

16.

Bjarnadottir T, Gloriam D, Hellstrand S, Kristiansson H, Fredriksson R, Schioth H . Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics. 2006; 88(3):263-73. DOI: 10.1016/j.ygeno.2006.04.001. View

17.

Nie T, Hui X, Gao X, Li K, Lin W, Xiang X . Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function. FEBS Lett. 2012; 586(20):3618-25. DOI: 10.1016/j.febslet.2012.08.006. View

18.

Kaur H, Carvalho J, Looso M, Singh P, Chennupati R, Preussner J . Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system. Nat Commun. 2017; 8:15700. PMC: 5481776. DOI: 10.1038/ncomms15700. View

19.

Lakso M, Pichel J, Gorman J, Sauer B, Okamoto Y, Lee E . Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A. 1996; 93(12):5860-5. PMC: 39152. DOI: 10.1073/pnas.93.12.5860. View

20.

Rentschler S, Jain R, Epstein J . Tissue-tissue interactions during morphogenesis of the outflow tract. Pediatr Cardiol. 2009; 31(3):408-13. PMC: 2951316. DOI: 10.1007/s00246-009-9611-2. View