The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila
Fernando Vieira Contreras,
Genevieve M. Auger,
Lena Müller,
Vincent Richter,
Wolf Huetteroth,
Florian Seufert,
Peter W. Hildebrand,
Nicole Scholz,
Andreas S. Thum,
Dmitrij Ljaschenko,
Beatriz Blanco-Redondo,
Tobias Langenhan
Affiliations
Fernando Vieira Contreras
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
Genevieve M. Auger
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
Lena Müller
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
Vincent Richter
Institute of Biology, Department of Genetics, Faculty of Life Sciences, Leipzig University, Talstraße 33, 04103 Leipzig, Germany
Wolf Huetteroth
Institute of Biology, Department of Genetics, Faculty of Life Sciences, Leipzig University, Talstraße 33, 04103 Leipzig, Germany
Florian Seufert
Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Härtelstrasse 16-18, 04107 Leipzig, Germany
Peter W. Hildebrand
Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Härtelstrasse 16-18, 04107 Leipzig, Germany
Nicole Scholz
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
Andreas S. Thum
Institute of Biology, Department of Genetics, Faculty of Life Sciences, Leipzig University, Talstraße 33, 04103 Leipzig, Germany
Dmitrij Ljaschenko
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
Beatriz Blanco-Redondo
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany; Corresponding author
Tobias Langenhan
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany; Institute of Biology, Faculty of Life Sciences, Leipzig University, Talstraße 33, 04103 Leipzig, Germany; Comprehensive Cancer Center Central Germany (CCCG), Germany; Corresponding author
Summary: Adhesion G-protein-coupled receptors (aGPCRs) form a large family of cell surface molecules with versatile tasks in organ development. Many aGPCRs still await their functional and pharmacological deorphanization. Here, we characterized the orphan aGPCR CG11318/mayo of Drosophila melanogaster and found it expressed in specific regions of the gastrointestinal canal and anal plates, epithelial specializations that control ion homeostasis. Genetic removal of mayo results in tachycardia, which is caused by hyperkalemia of the larval hemolymph. The hyperkalemic effect can be mimicked by a raise in ambient potassium concentration, while normal potassium levels in mayoKO mutants can be restored by pharmacological inhibition of potassium channels. Intriguingly, hyperkalemia and tachycardia are caused non-cell autonomously through mayo-dependent control of enterocyte proliferation in the larval midgut, which is the primary function of this aGPCR. These findings characterize the ancestral aGPCR Mayo as a homeostatic regulator of gut development.
