Ecosystem
Beta Site
Session VII
Physiological and pathological roles of AGPCRs in the nervous system
Uncovering the signaling pathway of the ADGRA homolog Remoulade in Drosophila
Beatriz Blanco Redondo
Abstract
"The Drosophila genome contains five loci encoding adhesion G-protein coupled receptors (aGPCRs). Phylogenetic analysis revealed that the remoulade (remo) gene is a homologue of the vertebrate aGPCR ADGRA family, sharing the same overall receptor domain structure.
In vivo expression profiling has shown Remo expression in the central (CNS) and peripheral nervous systems (PNS) of third-instar larvae (L3) and adults. In L3 PNS specimen Remo is expressed in a subset of neurons expressing the DEG/ENaC channel pickpocket (PPK), which is involved in transduction of sensory information like nociception. remoKO larvae and animals, in which remo was knocked down in ppk-neurons through RNA interference, show a higher nocifensive response compared to wildtype remorescue controls indicating that remo is required in PPK-neurons for this behaviour.
Furthermore, with the aim to analyse the biochemical properties of Remo, we performed immunoprecipitation analysis. We found that the receptor is cleaved despite the lack of a consensus GPS sequence. Hence, Remo is proteolytically processed, either by the GAIN domain or an alternative protease that cleaved Remo near the GPS.
We also aimed at identifying the signaling pathway that Remo is involved in. The mammalian Remo homolog ADGRA2/Gpr124 cooperates with other GPCRs of the Frizzled family, and the transmembrane proteins RECK and Lrp5/6. Collectively these proteins form a cell surface complex that acts as a recognition platform for Wnt ligands. Knowledge of the structural dynamics of this complex is limited and pharmacological and in vivo systems that would allow its characterization are scarce. Remo may serve a role in this peculiar signaling pathway and require further analysis."
Authors & Affiliations
"Auger, Genevieve Marie1, Bigl, Marina1, America, Michelle2, Vanhollebeke Benoit2, Langenhan Tobias1
1Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Johannisallee 30, 04103 Leipzig, Germany
2Laboratory of Neurovascular Signaling, Department of Molecular Biology, ULB Neuroscience Institute, Université libre de Bruxelles (ULB), Gosselies B-6041, Belgium"
About Beatriz Blanco Redondo
"I studied Biomedicine at the University of Barcelona. After my bachelors, I moved to Germany where I obtained my Master’s of Science and PhD degree in Dr. Buchner’s group at the University of Wuerzburg.
Shortly after receiving my PhD, I joined Dr. Neil Shneider’s group as a postdoctoral research scientist at Columbia University, New York, where I studied the mechanisms of motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS).
In 2017, I joined the group of Prof. Langenhan where I am studying and characterizing newly generated adhesion GPCR receptors in Drosophila as a model organism for future pharmacological applications."
Beatriz Blanco Redondo on the web
The Adhesion GPCR Latrophilin Interacts With The Notch Pathway To Control Germ Cell Proliferation
Willem Berend Post
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
"Groß Victoria Elisabeth 1, Matúš Daniel 2,3, Kaiser Anette 4, Ließmann Fabian 5, Meiler Jens 5, Schöneberg Torsten 2,6, Prömel Simone 1
1 Institute of Cell Biology, Department of Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
2 Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
3 Department of Molecular and Cellular Physiology, Stanford University, Stanford CA, USA
4 Department of Anaesthesiology and Intensive Care, Medical Faculty, Leipzig University, Leipzig, Germany
5 Institute for Drug Discovery, Faculty of Medicine, Leipzig University
6 School of Medicine, University of Global Health Equity, Kigali, Rwanda"
About Willem Berend Post
"Willem Berend Post is a PhD student in Cell Biology at Heinrich Heine University in Düsseldorf, Germany. His research focuses on the relevance of aGPCRs in physiology and signaling using both in vitro and in vivo approaches."