Session VIII *
Physiological and pathological roles of AGPCRs in the periphery
The CELSR/ADGRC Homolog Flamingo Is Not Autoproteolytically Processed By The GAIN Domain
Tobias Langenhan
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
"Tobias Langenhan, Nicole Scholz, Genevieve M. Auger, Helen Strutt, David Strutt"
About Tobias Langenhan
"1997-2004: Medical school and Dr. med. Neuroanatomy (Würzburg, Germany); 2004-2005: M.Sc. Neuroscience (Oxford, UK); 2005-2009: D.Phil. Neuroscience (Oxford, UK); 2009-2016: Group leader, Institute of Neurophysiology (Würzburg, Germany); 2016: Heisenberg professorship (Würzburg, Germany); 2016-to date: Professor and Chair in Biochemistry (Leipzig, Germany)"
Tobias Langenhan on the web
Characterization of Phenotypes Associated with GPR110 Deletion
Hee-Yong Kim
Abstract
"G-protein coupled receptor 110 (ADGRF1, GPR110), an adhesion GPCR recently deorphanized, plays an important role in in the development of neurons and cognitive function. Synaptamide, an endogenous ligand for GPR110, binds to the N-terminal G-protein autoproteolysis-inducing (GAIN) domain of GPR110, and activates GPR110/cAMP signaling. This activation promotes neurogenic differentiation of neural stem cells, neurite growth, and synaptogenesis of developing neurons. In addition, a significant role of GPR110 in blood brain barrier (BBB) function has been discovered. GPR110 is highly expressed in mouse and human NPCs and neurons, while its expression was absent in astrocytes. GPR110 is also highly expressed in the kidney, however, little is known about the function of this receptor in renal physiology. To extend our understanding of the role of GPR110 signaling in kidney, we evaluated the urine albumin level in mice devoid of GPR110 gene (GPR110 KO) compared to the wild type (WT). To provide the molecular basis for the renal phenotype, we analyzed in parallel differential expression of kidney proteins in GPR110 KO and WT mice by label-free LC-MS/MS and pathway analysis. We found that the albumin to creatinine ratio was significantly elevated in urine samples obtained from GPR110 KO mice, indicating glomerular filtration dysfunction. The change in protein expression of key proteins including VEGFA is associated with the abnormal renal phenotype of albumin urea in GPR110 KO mice. In addition to the central nervous system phenotype such as learning and memory deficit and BBB dysfunction, our study revealed a new renal phenotype associated with lack of GPR110 signaling. "
Authors & Affiliations
"Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, USA"
About Hee-Yong Kim
"Senior Investigator and Chief of the Laboratory of Molecular Signaling at NIAAA, NIH"
Hee-Yong Kim on the web
The Adhesion GPCR Cupidon Regulates Mating In The Closest Relatives Of Animals
Alain Garcia De Las Bayonas
Abstract
"All animals develop through the recognition, adhesion, and fusion of a differentiated sperm and egg. Although fundamental, the evolution of gametogenesis and fertilization in animals is poorly understood. Recently, evidence for sex has been described in choanoflagellates, the closest living relatives of animals. Under nutrient depletion, the model choanoflagellate Salpingoeca rosetta forms distinct cell types that aggregate, fuse, and undergo meiotic recombination. Additionally, the bacterium Vibrio fischeri also induces mating in S. rosetta cultures, suggesting that multiple environmental cues can trigger sex. Importantly, the signaling pathways underlying sexual reproduction in these different contexts have not been investigated.
In this study, we report the discovery of an adhesion GPCR, named Cupidon, that regulates the switch from vegetative growth to sexual reproduction in S. rosetta. We found that the knock-out of cupidon induces a gain in cell adhesion and cell fusion, resembling the mating behavior of wild-type cells under nutrient depletion. Cupidon mutants, similar to starved wild-type cells, upregulate various extracellular matrix-related genes, including teneurins and metalloproteases. Finally, we showed that nutrient availability controls the dissociation of the N-terminal fragment in Cupidon.
Together, our results suggest that Cupidon prevents sexual reproduction in S. rosetta under high nutrient availability, by inhibiting genes involved in gamete recognition. "
Authors & Affiliations
"King Nicole, Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California Berkeley"
About Alain Garcia De Las Bayonas
"Hi everyone! I am currently finishing my postoc in the laboratory of Pr Nicole King at UC Berkeley where I am studying the evolution of GPCR families in choanoflagellates, the sister group of animals. I have a particular interest in understanding the premetazoan function of adhesion GPCRs."
Alain Garcia De Las Bayonas on the web
Critical role for CD97/ADGRE5 in the induction of allergic airway inflammation
Gabriela Aust
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
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About Gabriela Aust
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Gabriela Aust on the web
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