title: Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning.
abstract: G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-αo47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-αo47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions.
authors.affiliation: Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
authors.forename: Meghna V
authors.initials: MV
authors.lastname: Patel
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Zhu
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Richman
authors.affiliation: Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
authors.forename: Mark F A
authors.initials: MF
authors.lastname: VanBerkum
authors.affiliation: Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010, USA. Electronic address: ZHan@childrensnational.org.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001011:Aorta / Q000196:embryology*; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D006321:Heart / Q000196:embryology*; D009024:Morphogenesis; D010496:Pericardium / Q000166:cytology / Q000196:embryology*; D010641:Phenotype; D025941:Protein Interaction Mapping; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C000621734:Mthl5 protein, Drosophila; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins
keywords: Drosophila; G protein coupled receptor; Gia; Heart development; Methuselah-like