Ecosystem
Beta Site
Adhesion GPCR workshop 2024
CINVESTAV, Mexico City, Mexico
October 23-25
Student Flash Presentations
Health and Disease, Metabolism, Nervous System, Proteomics and Transcriptomics, Receptor Structure, Signaling and Activation Mechanism
Adgrg6/Gpr126 is Required for Myocardial Notch Activity and N-cadherin Localization to Attain Trabecular Identity
Abhishek Kumar Singh
Abstract
Only available for AGPCR 24 Workshop Attendees
Authors & Affiliations
"Srivastava, Swati1; Singh, Abhishek Kumar1; Gunawan, Felix2; Gentile, Alessandra2; Petersen, Sarah C.3; Stainier, Didier Y.R.2; Engel, Felix B.1
1 Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Kussmaulallee 12, 91054 Erlangen, Germany
2 Developmental Genetics, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
3 Department of Developmental Biology, Washington University in St. Louis, 660 S. Euclid Ave, St. Louis, MO 63108, USA. Present address: Department of Neuroscience, Kenyon College, 203 North College Road, Gambier, OH 43022, USA"
About Abhishek Kumar Singh
"I am a doctoral student in the lab of Prof. Felix B. Engel. Since my undergraduate studies, I became fascinated with the class of adhesion GPCRs, owing to their potential, scarcity of knowledge on them, diverse expression profile, and the complexity with which they seem to be working. This made me pursue my higher education in the field of adhesion GPCRs. Accordingly, I worked with Prof. Hsi-Hsien Lin as summer intern twice, and finally joined the lab of Prof. Engel. I hope to develop my skillsets so as to be able to establish my own lab in future to work on adhesion GPCRs employing highly interdisciplinary field."
Abhishek Kumar Singh on the web
Investigating The Role of ADGRB3 Loss of Expression in Brain Tumor Formation in Li-Fraumeni Syndrome
Alex Torrelli-Diljohn
Abstract
"Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome caused by a germline mutation in the TP53 tumor suppressor gene. Glioblastoma (GBM) is the most prevalent central nervous system tumor in LFS, with TP53 mutations detected in 30% of sporadic GBMs. GBM is the most aggressive primary brain neoplasm that affects adults, with a median survival of 12-15 months. Recent studies implicate the dysregulation of adhesion G-Protein coupled receptors (GPCRs) in GBM development. Brain angiogenesis inhibitor 3 (BAI3/ADGRB3), a member of the BAI1-3 subfamily of adhesion GPCRS, has been observed to have low expression in brain tumors according to TCGA data, but the significance of this observation has not been explored. However, while its sister protein BAI1 has demonstrated tumor suppressor functions in the brain, it remains unclear whether BAI3 shares this role. To test this, an LFS mouse model (germline Tp53 deletion) with a second floxed allele under the control of Nestin-Cre was crossed to Bai3-/- mice. Preliminary findings indicate that the simultaneous loss of Bai3 and Tp53 expression in our mouse model increased spontaneous brain tumor formation incidence from 34% to 71%, in contrast to the loss of p53 alone. These observations lead me to hypothesize that ADGRB3 functions as a tumor suppressor in the brain, and its silencing, in the context of p53 mutation, facilitates GBM formation. Isolated GBM stem cells were collected for further genomic analyses and to test whether overexpression of BAI3 will save the tumor phenotype."
Authors & Affiliations
"van den Boom, Vincent; Pereira-Martins, Diego; Sheveleva, Sofia; Huls, Gerwin; Schuringa, Jan Jacob
Univerisity Medical Center Groningen"
About Alex Torrelli-Diljohn
"Alex completed his undergraduate & master’s degrees in Neurobiology & Cognitive sciences from the University of South Florida, where he researched early-onset Alzheimer’s disease in the lab of Dr. Angele Parent. He is interested in working on Li-Fraumeni syndrome and helping patients afflicted with this condition. He is also interested in working on Glioma Brain Organoid models."
Alex Torrelli-Diljohn on the web
GPR124 Mediates Adhesion Of Leukemic Stem Cells To Their Niche And Leads To Myeloid Skewing
Emmanouil Kyrloglou
Abstract
Only available for AGPCR 24 Workshop Attendees
About Emmanouil Kyrloglou
"Studied medicine at the University of Groningen. Now PhD-candidate at the Experimental Hematology lab of the University Medical Center Groningen (UMCG)."
Emmanouil Kyrloglou on the web
A single cell GPCR map of thermogenic fat
Vasiliki Karagiannakou
Abstract
Only available for AGPCR 24 Workshop Attendees
Authors & Affiliations
"Karagiannakou Vasiliki, El Merahbi Rabih, Herzig Stephan , Georgiadi A , Helmholtz Center Munich, Institute of Diabetes and Cancer"
About Vasiliki Karagiannakou
"MSc in Bioinformatics, PhD student since 2022 in the Institute for Diabetes and Cancer IDC, Helmholtz Centre Munich"
Vasiliki Karagiannakou on the web
GAIN Domain Dynamics And Its Relevance For Adhesion GPCR Signaling In Vivo
Lara-Sophie Brodmerkel
Abstract
"Over the last years, Adhesion G Protein-coupled receptors (aGPCR) have been shown to play a crucial role in the perception of mechanical signals. However, the molecular details underlying their activation and how mechanical forces are translated into an intracellular response remains largely unknown. Recent Molecular Dynamics (MD) simulations of several aGPCRs predicted two flexible regions, termed flaps, located within the GPCR autoproteolysis inducing (GAIN) domain. These flaps could theoretically enable partial decryption of the Stachel through lateral movement and affect activation of the receptor independent of NTF-CTF dissociation. However, the physiological relevance of flap flexibility on receptor activation and signaling remains unclear. To investigate whether flexibility of GAIN flaps affects aGPCR function under native conditions, we strategically inserted specific mutations into the GAIN domain of the Latrophilin homologue Cirl in Drosophila melanogaster, with the intention to alter flap dynamics. Our goal is to understand if and how flap dynamics influence Cirl function and consequently the mechanosensory faculty of neurons in vivo. To this end, we combine behavioral, biochemical, immunohistochemical and functional readouts, with the overarching ambition to expand our knowledge on the mechanistic details underlying aGPCR activation in mechanosensation."
Authors & Affiliations
"Brodmerkel Lara-Sophie 1, Bormann Anne 1, Seufert Florian 2, Hildebrand Peter 2,3 ´, Ljaschenko Dmitrij 1´, Scholz Nicole 1´
1Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany
2Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Leipzig, Germany
3Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Berlin, Germany
´ correspondence: scholzlab@gmail.com, Dmitrij.Ljaschenko@medizin.uni-leipzig.de, peter.hildebrand@medizin.uni-leipzig.de
*contributed equally"
About Lara-Sophie Brodmerkel
"I am a medical student and I´m currently working on my MD thesis in the lab of Dr. Nicole Scholz. We are investigating the relevance of GAIN domain dynamics for aGPCR signaling in Drosophila melanogaster."
Lara-Sophie Brodmerkel on the web
Novel isoforms of adhesion GPCR B1 (ADGRB1/BAI1) generated from an alternative promoter in intron 17
Rashed Rezwan Parag
Abstract
"Brain-specific angiogenesis inhibitor 1 (BAI1) belongs to the adhesion G-protein-coupled receptors, which exhibit large multi-domain extracellular N-termini that mediate cell-cell and cell-matrix interactions. To explore the existence of BAI1 isoforms, we queried genomic datasets for markers of active chromatin and new transcript variants in the ADGRB1 (adhesion G protein-coupled receptor B1) gene. Two major types of mRNAs were identified in human/mouse brain, those with a start codon in exon 2 encoding a full-length protein of a predicted size of 173.5/173.3 kDa and shorter transcripts starting from alternative exons at the intron 17/exon 18 boundary with new or exon 19 start codons, predicting shorter isoforms of 76.9/76.4 and 70.8/70.5 kDa, respectively. Immunoblots on wild-type and Adgrb1 exon 2-deleted mice, reverse transcription PCR and promoter-luciferase reporters confirmed that the shorter isoforms originate from an alternative promoter in intron 17. The shorter BAI1 isoforms lack most of the N-terminus and are very close in structure to the truncated BAI1 isoform generated through GPS processing from the full-length receptor. The cleaved BAI1 isoform has a 19 amino acid extracellular stalk that can serve as a receptor agonist, while the alternative transcripts generate BAI1 isoforms with extracellular N-termini of 5 or 60 amino acids. Further studies are warranted to compare the functions of these isoforms and examine the distinct roles they play in different tissues and cell types."
About Rashed Rezwan Parag
"Rashed is from Bangladesh. He has received his BSc and MS degree from the Department of Biochemistry and Molecular Biology, University of Chittagong, Bangladesh. Before joining UAB as a graduate student, he worked in the EuGEF Research Group to identify novel prognostic biomarkers and therapeutic options for Metastatic Breast Cancer (BC) and Head and Neck Squamous Cell Carcinoma (HNSCC). Currently, he is working to elucidate the role of ADGRB1 and ADGRB3 in medulloblastoma (pediatric brain tumor)."
Rashed Rezwan Parag on the web
Identification of Differentially Expressed Gpr116 (Adgrf5) Transcript Variants in Mouse Kidney
Hailey Steichen
Abstract
"Adhesion G protein-coupled receptors (aGPCRs) are important and understudied modulators of physiological processes. Previous work suggests that aGPCRs, and Adgrf5 in particular, undergo significant tissue-specific mRNA processing that results in holoreceptors with unique and variable N-terminal structures (Knierim et al. 2019). Recently, it was shown that transcripts of the postsynaptic aGPCR Latrophilin-3 (Lphn3/Adgrl3) undergo physiologically relevant alternative splicing, which determined heterotrimeric signaling through Gαs- or Gα12/13- mediated pathways (Südhof et al. 2024). These results demonstrate that identifying precise, tissue-specific transcript variants is critical to understanding the physiological relevance of aGPCRs. Moreover, these studies highlight the possibility that tissue expression of single aGPCRs is likely comprised of multiple transcript variants. We previously demonstrated that kidney-specific Adgrf5/Gpr116 knockout causes luminal membrane accumulation of V-ATPase in acid-secreting A-type intercalated cells (AICs) in the collecting ducts and a significant reduction in urine pH (Zaidman et al. 2020). Renal Adgrf5 is restricted to two distinct populations of cells: AICs and endothelial cells (ECs). We hypothesized that cell-specific Adgrf5 transcript variants are expressed in renal AICs and ECs, and therefore are activated by distinct mechanisms unique to the cellular microenvironment. We detected and aligned three Adgrf5 exons that undergo differential expression in the kidney: exons 2, 12, and 22. Adgrf5 transcripts in FACS-sorted GFP+ ICs do not contain the exon 2 variable region, or the alternative exons 12 and 22, while ECs contain all three. However, EC markers were detected in GFP+ ICs, demonstrating some EC contamination in the sorted ICs. Detection of transcripts that do, and do not, contain multiple variable regions suggests expression of multiple mRNAs in specific cells. These data demonstrate that Adgrf5 transcript variants are cell-specific in the kidney. Moreover, the complete repertoire of aGPCRs expressed in the kidney is undefined. We performed single-nucleus RNA sequencing on male and female kidneys. snRNAseq revealed abundant, cell-specific expression of six aGPCRs (Adgrl4, Adgre5, Adgrf1, Adgrf5, Adgrg1, and Adgrg3). Detection of these, as well as 18 other aGPCRs, was confirmed by PCR screening for GAIN/GPS domains on cDNA from whole-kidney lysates. These results reveal the complete set of aGPCRs expressed in the murine kidney. Future studies will focus on determining the physiological roles and tissue-specific variants of these receptors."
Authors & Affiliations
"Department of Biochemistry & Molecular Biology, University of New Mexico Health Sciences Center
Xue, Jianxiang; Yan, Teagan; Eaton, Krystin, and Zaidman, Nathan"
About Hailey Steichen
"I currently work in Dr. Nathan Zaidman’s lab at the University of New Mexico Health Sciences Center. I am researching the physiological relevance of Adgrf5 (Gpr116) transcript variants in specific cell types in the kidney. I have also worked in the laboratory of Dr. James Bridges at National Jewish Health in Denver, CO researching molecular mechanisms of lung injury and repair mediated by Adgrf5. I received my MS in Applied Toxicology from the University of Washington, and my BA in Biology from Vassar College."
Hailey Steichen on the web
Elucidating The Role Of GPR97/ADGRG3 In Neutrophil Biology
Tyler Bernadyn
Abstract
Only available for AGPCR 24 Workshop Attendees
Authors & Affiliations
"Gandhi, Riya; Chandan, Nancy; Kwarcinski, Frank; Smrcka, Alan; and Tall, Gregory G."
About Tyler Bernadyn
"4th year Pharmacology Ph.D. Student in Greg Tall's Lab."