Ecosystem
Beta Site
Session VII
Physiological and pathological roles of AGPCRs in the nervous system
Adhesion G protein-coupled receptor latrophilin-3 (ADGRL3) modulation of dopaminergic neurotransmission
Nicole Perry-Hauser
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
"Nicole A. Perry-Hauser1,2, Arturo Torres Herraez1,2, Dan Lowes1,2, Ying Zhu1,2, Siham Boumhaouad1,3, Eugene V. Mosharov1,2,4, David Sulzer1,2,4, Christoph Kellendonk1,2, and Jonathan A. Javitch1,2
1Departments of Psychiatry and Molecular Pharmacology and Therapeutics, Columbia University, New York, NY 10032; 2Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032; 3 Physiology and Physiopathology, Faculty of Sciences, Mohammed V University, Rabat 1014, Morocco; 4Department of Neurology, Columbia University, New York, NY 10032"
About Nicole Perry-Hauser
"I am an associate research scientist endeavoring to build a productive, independent scientific research career in adhesion G protein-coupled receptor (aGPCR) biology. My long-term research interests involve resolving signaling pathways downstream of aGPCRs and establishing how/if these receptors’ adhesive properties influence signaling events, and in turn whether signaling impacts synapse formation and neuronal wiring. I initially became interested in GPCR signal transduction during my graduate training in the Department of Pharmacology at Vanderbilt University where I studied under the co-mentorship of Dr. Vsevolod V. Gurevich and Dr. Tina M. Iverson. I then pursued a postdoctoral research position under the mentorship of Dr. Jonathan A. Javitch in the Department of Psychiatry at Columbia University Irving Medical Center."
Nicole Perry-Hauser on the web
GPR110 modulates anxiety-like behaviors and memory function in mice potentially through neuronal and neuroimmune alterations during neurodevelopment
Mariam Melkumyan
Abstract
"GPR110, an adhesion G protein coupled receptor (GPCR), is widely expressed in developing brains but diminishes in adult stage except in the hippocampus, a region involved in learning and memory. Ligand-induced GPR110 signaling stimulates neurogenesis and synaptogenesis during development, and the absence of the ligand-induced signaling causes object recognition and spatial memory deficits in adulthood and increased neuroinflammatory responses. Nevertheless, the role of GPR110 signaling in behavioral consequences has not been fully explored.
This study aimed to understand the effects of GPR110 on mouse behaviors in relation to neurodevelopmental and neuroimmune gene and protein expression. Anxiety and memory function were tested using both male and female mice at 5-6 month of age. GPR110 knockout (KO) mice displayed trends for increased anxiety-like behaviors in the elevated plus maze test and in the open field test. Memory tests, including the novel object test and the radial 8-arm maze showed worsened spatial and reference memory in the GPR110 KO mice compared to wildtype mice. The y-maze showed a significant sex by genotype interactions with GPR110 KO male mice having increased number of correct alterations and errors, while the GPR110 KO females had fewer correct alterations and errors.
RNAseq data indicated significantly impaired developmental gene expression for neuronal differentiation, axonogenesis, and synaptogenesis, as well as altered neuroinflammatory marker expression in GPR110 KO mouse brains. Further studies exploring the protein expression and neural activity of these mouse brain will give insight on the mechanism underlying the behavioral consequences associated with the GPR110 receptor. "
Authors & Affiliations
"Joel Toro, Bill Huang, Hee-Yong Kim
Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, NIH"
About Mariam Melkumyan
"Mariam Melkumyan is a postdoctoral fellow at the Laboratory of Molecular Signaling studying the role of GPR110 in neurotransmission and neuroimmune activity involved in learning and memory, anxiety, and alcohol use. Mariam, originally from Armenia, completed her bachelor's degree in Neuroscience at American University in Washington, DC and her dual-title PhD in Neuroscience and Clinical and Translational Sciences at Penn State College of Medicine in Hershey, PA. Mariam started her postdoctoral training in February 2024 and is hoping to become an academic professor and mentor the next generation of scientists."
Mariam Melkumyan on the web
Adhesion G protein-coupled receptor ADGRG1 promotes protective microglial response in Alzheimer’s disease
Xianhua Piao
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
"Beika Zhu, UCSF
Andi Wangzhou, UCSF
Diankun Yu, UCSF"
About Xianhua Piao
"My research follows the bedside-to-bench-to-bedside paradigm. I began by characterizing an autosomal recessive human brain malformation that my mentor Chris Walsh and I termed bilateral frontoparietal polymicrogyria (BFPP). Together, we discovered that germline loss-of-function mutations in the adhesion G-protein-coupled receptor (aGPCR) GPR56, also called ADGRG1, cause BFPP. Over time, this discovery transformed our understanding of polymicrogyria and yielded a molecular diagnosis (https://blueprintgenetics.com/tests/panels/malformations/polymicrogyria-panel). Following the thread of GPR56 biology also led me to a vigorous bench research program. We've steadily uncovered a remarkable diversity of cell type- and ligand-specific functions of GPR56 during various stages of brain development and homeostasis, including cortical patterning, central nervous system myelin formation and repair, and synaptic refinement. In doing so, I undertook a pioneering role in deorphanizing aGPCRs and revealing mechanisms underlying aGPCR-mediated cell-cell and cell-matrix interactions. This basic science also provides foundational knowledge for drug discoveries in targeting aGPCRs, the second largest human GPCR family."
Xianhua Piao on the web
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."