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Your search keyword '"Genevieve M. Auger"' showing total 3 results
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3 results on '"Genevieve M. Auger"'

1. The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila

Author

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, and Tobias Langenhan

Subjects
CP: Developmental biology, Biology (General), QH301-705.5
Abstract

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.

Published
2024
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2. Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation

Author

Nicole Scholz, Anne-Kristin Dahse, Marguerite Kemkemer, Anne Bormann, Genevieve M. Auger, Fernando Vieira Contreras, Lucia F. Ernst, Hauke Staake, Marek B. Körner, Max Buhlan, Amelie Meyer-Mölck, Yin Kwan Chung, Beatriz Blanco-Redondo, Franziska Klose, Mohamed Ali Jarboui, Dmitrij Ljaschenko, Marina Bigl, and Tobias Langenhan

Subjects
Multidisciplinary
Published
2023

3. The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release

Author

Mila M Paul, Sven Dannhäuser, Lydia Morris, Achmed Mrestani, Martha Hübsch, Jennifer Gehring, Georgios N Hatzopoulos, Martin Pauli, Genevieve M Auger, Grit Bornschein, Nicole Scholz, Dmitrij Ljaschenko, Martin Müller, Markus Sauer, Hartmut Schmidt, Robert J Kittel, Aaron DiAntonio, Ioannis Vakonakis, Manfred Heckmann, and Tobias Langenhan

Subjects
Cognition, Drosophila melanogaster, Mutation, Presynaptic Terminals, Animals, Humans, Drosophila Proteins, Neurology (clinical), Synaptic Transmission, Retinitis Pigmentosa
Abstract

Humans carrying the CORD7 (cone-rod dystrophy 7) mutation possess increased verbal IQ and working memory. This autosomal dominant syndrome is caused by the single-amino acid R844H exchange (human numbering) located in the 310 helix of the C2A domain of RIMS1/RIM1 (Rab3-interacting molecule 1). RIM is an evolutionarily conserved multi-domain protein and essential component of presynaptic active zones, which is centrally involved in fast, Ca2+-triggered neurotransmitter release. How the CORD7 mutation affects synaptic function has remained unclear thus far. Here, we established Drosophila melanogaster as a disease model for clarifying the effects of the CORD7 mutation on RIM function and synaptic vesicle release. To this end, using protein expression and X-ray crystallography, we solved the molecular structure of the Drosophila C2A domain at 1.92 Å resolution and by comparison to its mammalian homologue ascertained that the location of the CORD7 mutation is structurally conserved in fly RIM. Further, CRISPR/Cas9-assisted genomic engineering was employed for the generation of rim alleles encoding the R915H CORD7 exchange or R915E, R916E substitutions (fly numbering) to effect local charge reversal at the 310 helix. Through electrophysiological characterization by two-electrode voltage clamp and focal recordings we determined that the CORD7 mutation exerts a semi-dominant rather than a dominant effect on synaptic transmission resulting in faster, more efficient synaptic release and increased size of the readily releasable pool but decreased sensitivity for the fast calcium chelator BAPTA. In addition, the rim CORD7 allele increased the number of presynaptic active zones but left their nanoscopic organization unperturbed as revealed by super-resolution microscopy of the presynaptic scaffold protein Bruchpilot/ELKS/CAST. We conclude that the CORD7 mutation leads to tighter release coupling, an increased readily releasable pool size and more release sites thereby promoting more efficient synaptic transmitter release. These results strongly suggest that similar mechanisms may underlie the CORD7 disease phenotype in patients and that enhanced synaptic transmission may contribute to their increased cognitive abilities.

Published
2022

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