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*

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number113640
Number of pages20
JournalCell Reports
Volume43
Issue number1
Early online date4 Jan 2024
DOIs
Publication statusPublished - 23 Jan 2024
Externally publishedYes

Keywords

  • adhesion GPCR
  • cardiac physiology
  • CP: Developmental biology
  • Drosophila melanogaster
  • GAIN domain
  • gut
  • potassium homeostasis

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