Ecosystem
Beta Site
Session II
AGPCR signaling pathways and trafficking
Localization of putative ligands for adhesion G protein-coupled receptors in mouse tissues.
Yuling Feng
Abstract
Only available for AGPCR 24 Workshop Attendees
Authors & Affiliations
"Shen,Tingzhen; Bernadyn,Tyler; Kwarcinski, Frank; Gandhi, Riya; Tall, Greg. University of Michigan."
About Yuling Feng
"I am currently a postdoctoral research fellow working with aGPCR pharmacology and physiology in rodents."
Yuling Feng on the web
The ADGRF5/GPR116 receptor is a key regulator of lymphatic endothelial cell identity and function
Monserrat Avila Zozaya
Abstract
Only available for AGPCR 24 Workshop Attendees
Authors & Affiliations
"Serafin D. Stephen, Caron Kathleen M
Department of Cell Biology and Physiology at UNC Chapel Hill 111 Mason Farm Road, MBRB, CB 7545. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA 27599"
About Monserrat Avila Zozaya
"My doctoral research was focused on investigating the cellular effects of missense lung cancer-mutations in the G-protein-coupled receptor Autoproteolysis-Inducing (GAIN) domain of Latrophilin 3 receptor under the mentorship of Dr. Antony Boucard.
I am currently a postdoctoral researcher fellow in Dr. Kathleen Caron's laboratory at UNC. My research focuses on understanding the molecular mechanisms of adhesion GPCRs (aGPCRs) in lymphatic endothelial cells (LECs), a cellular model with unique junction arrangements where aGPCRs are mainly unexplored. "
Monserrat Avila Zozaya on the web
Adhesion GPCR BAI1/ADGRB1 can block IGF1R-mediated growth signalling, increase radiosensitivity and augment survival in medulloblastoma.
Erwin G. Van Meir
Abstract
Only available for AGPCR 24 Attendees
Authors & Affiliations
"Yamamoto, Takahiro 1,2*, De Araujo Farias, Virginea 1, Zhu, Dan3; Kuranaga, Yuki1, Parag, Rashed Rezwan 1,4,, Osuka, Satoru1,5
1 Department of Neurosurgery, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
2 Department of Neurosurgery, Kumamoto University, Kumamoto, Japan
3 Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA
4 Graduate Biomedical Sciences, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA
5 O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA "
About Erwin G. Van Meir
"Dr. Erwin Van Meir is a professor in the UAB Department of Neurosurgery. He was trained in molecular biology at the Universities of Fribourg and Lausanne, Switzerland where he obtained his Ph.D. in 1989. Dr. Van Meir pursued postdoctoral work at the Ludwig Institute for Cancer Research in San Diego and joined the faculty of Emory University in 1998.
His research interest lies in understanding the molecular basis for human tumor development and how to use this knowledge to devise new therapeutics that will improve patient survival. Van Meir’s research examines how genetic alterations and hypoxia induce changes in cell biology that promote tumor formation with particular emphasis on adhesion GPCRs ADGRB1 and ADGRB3. Van Meir has developed novel therapeutic approaches for cancer using oncolytic adenoviruses and anti-angiogenic molecules and is currently developing novel small molecule inhibitors of the hypoxia-inducible factor pathway and the epigenetic reader MBD2 (methyl CpG binding protein 2). His research aims to translate these novel agents to testing in clinical trials with the hope to develop novel medicines for cancer treatment."
Erwin G. Van Meir on the web
Site Specific N-Glycosylation Of The N-Terminal Fragment Of ADGRG6 Drives Proteolytic Processing, Trafficking And Signalling
Pal Kasturi
Abstract
"ADGRG6 is a member of the adhesion G-protein-coupled receptor (aGPCR) family, known to play a role in myelination, placentation, blood vessel, and inner ear development. Like many other aGPCRs, ADGRG6 undergoes autoproteolysis at the GPCR-autoproteolysis site (GPS) enclosed within the larger GAIN domain to generate the N-terminal (NTF) and C-terminal fragments (CTF). These cleaved fragments join to form the heteromeric ADGRG6 receptor complex. ADGRG6 NTF has multiple extracellular domains like CUB, PTX, SEA, hormone binding domain, and the GAIN domain, which regulate G-protein signaling by binding to extracellular matrix proteins and mechanotransduction. The short stachel sequence at the extreme N-terminal end of the CTF functions as a tethered agonist to activate cAMP signaling. GPCR signaling and trafficking can be regulated by several different post-translational modifications (PTM). Stehlik et al. have reported that ADGRG6 expressed in lipopolysaccharide stimulated human umbilical vein endothelial cells is N-glycosylated. However, it is unclear which domains of ADGRG6 are N-glycosylated and how this might affect the overall molecular pharmacology of the receptor. Furthermore, are there spatial roles of N-glycosylation in ADGRG6 processing, trafficking, signalling and in-vivo functions? To address these gaps in knowledge, we used biochemical and cell-biological approaches using cell-lines overexpressing wild-type and N-glycosylation mutants of ADGRG6. We observed that N-glycosylation specifically takes place in the NTF and not the CTF of ADGRG6. Our results demonstrate that specific N-glycan residues in different domains of the extracellular NTF of ADGRG6 have distinct roles in ADGRG6 autoproteolysis, furin cleavage, membrane trafficking, and G-protein signalling. In the future, we plan to decipher the roles of N-glycosylation of ADGRG6 in organogenesis and tissue development using zebrafish models."
Authors & Affiliations
"Anandhu Jayaraman: Department of Biology, Ashoka University
Prabakaran Annadurai: Department of Biology, Ashoka University. Currently: University of Leipzig
Mansi Tiwari: Department of Biology, Ashoka University. Currently: University of Aberdeen
Priyadatha Sajan: Department of Biology, Ashoka University, Currently: University of Groningen
Nayonika Chatterjee: Department of Biology, Ashoka University
Prateek Sibal: Department of Biology, Ashoka University"
About Pal Kasturi
"I received my bachelor’s degree in Physiology from Presidency College, University of Calcutta and went on to complete my masters from Madurai Kamaraj University. During my PhD training, I worked in the laboratory of Dr. Kathryn Defea at the University of California, Riverside. For my PhD thesis, I worked on non-canonical, scaffold driven signaling by protease activated receptor-2 (PAR2). I joined University of Texas Southwestern Medical Center, for my postdoctoral training. Here, I worked on the regulation of the Sonic Hedgehog pathway by GPCRs which localized to the primary cilia. I then joined the laboratory of Dr. Velia Fowler, at the Scripps Research Institute, as a Judith Graham Poole postdoctoral fellow to work on the role of cytoskeletal proteins in megakaryocyte to platelet differentiation. I joined the Department of Biology at Ashoka University in 2020 as an assistant professor."