A screen of pharmacologically active compounds to identify modulators of the Adgrg6/Gpr126 signalling pathway in zebrafish embryos

Asad A, Shahidan NO, de la Vega de León A, Wiggin GR, Whitfield TT, Baxendale  S

Basic Clin Pharmacol Toxicol. 2023 Oct

doi: 10.1111/bcpt.13923.

Adhesion G Protein-Coupled Receptor Gpr126 (Adgrg6) Expression Profiling in Diseased Mouse, Rat, and Human Kidneys

Kösters P, Cazorla-Vázquez S, Krüger R, Daniel C, Vonbrunn E, Amann K, Engel FB

Cells. 2024 May 18

doi: 10.3390/cells13100874.

Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation

Scholz N, Dahse A, Kemkemer M, Bormann A, Auger GM, Contreras FV, Ernst LF, Staake H,  Körner MB, Buhlan M, Meyer-Mölck A, Chung YK, Blanco-Redondo B, Klose F, Jarboui MA, Ljaschenko D, Bigl M, Langenhan T

Nature. 2023 Mar

doi: 10.1038/s41586-023-05802-5.

Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs

Fu C, Huang W, Tang Q, Niu M, Guo S, Langenhan T, Song G, Yan J

Nano Lett. 2023 Oct

doi: 10.1021/acs.nanolett.3c01163.

Optimized genetic code expansion technology for time-dependent induction of adhesion GPCR-ligand engagement

Streit M, Hemberger M, Häfner S, Knote F, Langenhan T, Beliu G

Protein Sci. 2023 Apr

doi: 10.1002/pro.4614.

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity

Dietzsch AN, Al-Hasani H, Altschmied J, Bottermann K, Brendler J, Haendeler J, Horn S, Kaczmarek I, Körner A, Krause K, Landgraf K, Le Duc D, Lehmann L, Lehr S, Pick S, Ricken A, Schnorr R, Schulz A, Strnadová M, Velluva A, Zabri H, Schöneberg T, Thor D, Prömel S

Signal Transduct Target Ther. 2024 Apr 26

doi: 10.1038/s41392-024-01810-7.

Downstream signalling of the disease-associated mutations on GPR56/ADGRG1

Cevheroğlu O, Demir N, Kesici MS, Özçubukçu S, Son CD

Basic Clin Pharmacol Toxicol. 2023 Apr 13

doi: 10.1111/bcpt.13873

Upregulation of mRNA Expression of ADGRD1/GPR133 and ADGRG7/GPR128 in SARS-CoV-2-Infected Lung Adenocarcinoma Calu-3 Cells

Žáčková S, Pávová M, Trylčová J, Chalupová J, Priss A, Lukšan O, Weber J

Cells. 2024 May 7

doi: 10.3390/cells13100791

Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment.

Köck Z, Schnelle K, Persechino M, Umbach S, Schihada H, Januliene D, Parey K, Pockes S, Kolb P, Dötsch V, Möller A, Hilger D, Bernhard F.

Nat Commun. 2024 Feb 28;15(1):1831

doi: 10.1038/s41467-024-46096-z.

Translating the force-mechano-sensing GPCRs

Wilde C, Mitgau J, Suchy T, Schöneberg T, Liebscher I

Am J Physiol Cell Physiol. 2022 Jun 1

doi: 10.1152/ajpcell.00465.2021.

Affinity Proteomics Identifies Interaction Partners and Defines Novel Insights into the Function of the Adhesion GPCR VLGR1/ADGRV1

Knapp B, Roedig J, Roedig H, Krzysko J, Horn N, Güler BE, Kusuluri DK, Yildirim A, Boldt K, Ueffing M, Liebscher I, Wolfrum U

Molecules 2022 May

doi: 10.3390/molecules27103108

The adhesion GPCR and PCP component flamingo (FMI-1) alters body size and regulates the composition of the extracellular matrix

Schön JL, Groß VE, Post WB, Daum A,  Matúš D, Pilz J, Schnorr R, Horn S, Bäumers M, Weidtkamp-Peters S, Hughes S, Schöneberg T, Prömel S

Matrix Biol. 2024 Feb 18

doi: 10.1016/j.matbio.2024.02.005.

Adhesion GPCR Gpr126 (Adgrg6) Expression Profiling in Zebrafish, Mouse, and Human Kidney

Cazorla-Vazquez S, Kösters P, Bertz S, Pfister F, Daniel C, Dedden M, Zundler S, Jobst-Schwan T, Amann K, Engel FB

Cells. 2023 Aug 2

doi: 10.3390/cells12151988.

The repertoire and structure of adhesion GPCR transcript variants assembled from publicly available deep-sequenced human samples

Kuhn CK , Stenzel U, Berndt S, Liebscher I, Schöneberg T, Horn S

Nucleic Acids Res. 2024 Apr 24

doi: 10.1093/nar/gkae145.

The dark sides of the GPCR tree - research progress on understudied GPCRs.

Scharf MM, Humphrys LJ, Berndt S, Di Pizio A, Lehmann J, Liebscher I, Nicoli A, Niv MY, Peri L, Schihada H, Schulte G. Br

J Pharmacol. 2024 Feb 10

doi: 10.1111/bph.16325.

Intramolecular activity regulation of adhesion GPCRs in light of recent structural and evolutionary information

Kleinau G, Ali AH, Wiechert F, Szczepek M, Schmidt A, Spahn CMT, Liebscher I, Schöneberg T, Scheerer P

Pharmacol Res. 2023 Oct 30

doi: 10.1016/j.phrs.2023.106971.

The N Terminus of Adhesion G Protein-Coupled Receptor GPR126/ADGRG6 as Allosteric Force Integrator

Mitgau J, Franke J, Schinner C, Stephan G, Berndt S, Placantonakis DG, Kalwa H, Spindler V, Wilde C, Liebscher I

Front Cell Dev Biol. 2022 Jun 23

doi: 10.3389/fcell.2022.873278.

Structural basis for the tethered peptide activation of adhesion GPCRs

Ping Y, Xiao P, Yang F, Zhao R, Guo S, Yan X, Wu X, Zhang C, Lu Y, Zhao F, Zhou F, Xi Y, Yin W, Liu F, He D, Zhang D, Zhu Z, Jiang Y, Du L, Feng S, Schöneberg T, Liebscher I, Xu EH, Sun J

Nature. 2022 Apr 13

doi: 10.1038/s41586-022-0419-y.

The posttraumatic increase in the Adhesion GPCR EMR2/ADGRE2 to circulating neutrophils is not related to injury severity.

Zheng L, Rang M, Fuchs C, Keß A, Wunsch M, Hentschel J, Hsiao CC, Kleber C, Osterhoff G, Aust G.

Cells. 2023 Nov 20;12(22):2657.

doi: 10.3390/cells12222657

CDK7/12/13 inhibition targets an oscillating leukemia stem cell network and synergizes with venetoclax in acute myeloid leukemia.

He L, Arnold C, Thoma J, Rohde C, Kholmatov M, Garg S, Hsiao CC, Viol L, Zhang K, Sun R, Schmidt C, Janssen M, MacRae T, Huber K, Thiede C, Hébert J, Sauvageau G, Spratte J, Fluhr H, Aust G, Müller-Tidow C, Niehrs C, Pereira G, Hamann J, Tanaka M, Zaugg JB, Pabst C.

EMBO Mol Med. 2022 Apr7;14(4):e14990.

doi: 10.15252/emmm.202114990

The Evolutionary History of Vertebrate Adhesion GPCRs and Its Implication on Their Classification

Wittlake A, Prömel S, Schöneberg T

Int J Mol Sci. 2021 Oct 30

doi: 10.3390/ijms222111803.

A guide to adhesion GPCR research.

Liebscher I, Cevheroğlu O, Hsiao CC, Maia AF, Schihada H, Scholz N, Soave M, Spiess K, Trajković K, Kosloff M, Prömel S.

FEBS J. 2021 Nov 2. Online ahead of print.

doi: 10.1111/febs.16258.

Adhesion GPCR GPR56 Expression Profiling in Human Tissues

Kaiser F, Morawski M, Krohn K, Rayes N, Hsiao C, Quaas M, Aust G

Cells. 2021 Dec 16

doi: 10.3390/cells10123557.

Phospholipid-flippase chaperone CDC50A is required for synapse maintenance by regulating phosphatidylserine exposure

Li T, Yu D, Oak HC, Zhu B, Wang L, Jiang X, Molday RS, Kriegstein A, Piao X

EMBO J. 2021 Nov 2

doi: 10.15252/embj.2021107915.

Latrophilin-1 drives neuron morphogenesis and shapes chemo- and mechanosensation-dependent behavior in C. elegans via a trans function

Matúš D, Post WB, Horn S, Schöneberg T, Prömel S

Biochem Biophys Res Commun. 2022 Jan 22

doi: 10.1016/j.bbrc.2021.12.006.

Mimicking extracellular matrix-mediated mechano-activation by antibodies to control signaling of the adhesion G protein-coupled receptor GPR126/ADGRG6.

Jakob Mitgau, Julius Franke, Camilla Schinner, Gabriele Stephan, Sandra Berndt, Dimitris G. Placantonakis, Hermann Kalwa, Volker Spindler, Caroline Wilde, Ines Liebscher.

doi: https://doi.org/10.1101/2021.09.13.460127

Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.

David M Favara, Ines Liebscher, Ali Jazayeri, Madhulika Nambiar, Helen Sheldon, Alison H Banham, Adrian L Harris.

Sci Rep. 2021 Apr 23;11(1):8870.

doi: 10.1038/s41598-021-85408-x

Functional impact of intramolecular cleavage and dissociation of adhesion G protein-coupled receptor GPR133 (ADGRD1) on canonical signaling.

Joshua D Frenster, Gabriele Stephan, Niklas Ravn-Boess, Devin Bready, Jordan Wilcox, Bjoern Kieslich, Caroline Wilde, Norbert Sträter, Giselle R Wiggin, Ines Liebscher, Torsten Schöneberg, Dimitris G Placantonakis.

Biol Chem. Jan-Jun 2021;296:100798.  Epub 2021 May 20.

doi: 10.1016/j.jbc.2021.100798.

Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes.

Frenster JD, Kader M, Kamen S, Sun J, Chiriboga L, Serrano J, Bready D, Golub D, Ravn-Boess N, Stephan G, Chi AS, Kurz SC, Jain R, Park CY, Fenyo D, Liebscher I, Schöneberg T, Wiggin G, Newman R, Barnes M, Dickson JK, MacNeil DJ, Huang X, Shohdy N, Snuderl M, Zagzag D, Placantonakis DG.

Neurooncol Adv. 2020 Apr 28;2(1):vdaa053.

doi: 10.1093/noajnl/vdaa053.

eCollection 2020 Jan-Dec

GPCRmd uncovers the dynamics of the 3D-GPCRome

Rodríguez-Espigares I; Mariona Torrens-Fontanals; Johanna K. S. Tiemann; David Aranda-García; Juan Manuel Ramírez-Anguita; Tomasz Maciej Stepniewski; Nathalie Worp; Alejandro Varela-Rial; Adrián Morales-Pastor; Brian Medel-Lacruz; Gáspár Pándy-Szekeres; Eduardo Mayol; Toni Giorgino; Jens Carlsson; Xavier Deupi; Slawomir Filipek; Marta Filizola; José Carlos Gómez-Tamayo; Angel Gonzalez; Hugo Gutiérrezde-Terán; Mireia Jiménez-Rosés; Willem Jespers; Jon Kapla; George Khelashvili; Peter Kolb; Dorota Latek; Maria Marti-Solano; Pierre Matricon; Minos-Timotheos Matsoukas; Przemyslaw Miszta; Mireia Olivella; Laura Perez-Benito; Davide Provasi; Santiago Ríos; Iván R. Torrecillas; Jessica Sallander; Agnieszka Sztyler; Silvana Vasile; Harel Weinstein; Ulrich Zachariae; Peter W. Hildebrand; Gianni De Fabritiis; Ferran Sanz; David E. Gloriam; Arnau Cordomi; Ramon Guixà-González; Jana Selent

Nature Methods 2020 Aug;17(8):777-787

DOI doi:10.1038/s41592-020-0884-y

The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors.

Morgan RK, Anderson GR, Araç D, Aust G, Balenga N, Boucard A, Bridges JP, Engel FB, Formstone CJ, Glitsch MD, Gray RS, Hall RA, Hsiao CC, Kim HY, Knierim AB, Kusuluri DK, Leon K, Liebscher I, Piao X, Prömel S, Scholz N, Srivastava S, Thor D, Tolias KF, Ushkaryov YA, Vallon M, Van Meir EG, Vanhollebeke B, Wolfrum U, Wright KM, Monk KR, Mogha A.

Ann N Y Acad Sci. 2019 Nov;1456(1):5-25.

doi: 10.1111/nyas.14094.

The repertoire of Adhesion G protein-coupled receptors in adipocytes and their functional relevance

Suchý T, Zieschang C, Popkova Y, Kaczmarek I, Weiner J, Liebing A, Çakir MV, Landgraf K, Gericke M, Pospisilik JA, Körner A, Heiker JT, Dannenberger D, Schiller J, Schöneberg T, Liebscher I, Thor D

Int J Obes (London). 2020 Mar 19

doi: 10.1038/s41366-020-0570-2

Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons

Del Toro D, Carrasquero-Ordaz MA, Chu A, Ruff T, Shahin M, Jackson VA, Chavent M, Berbeira-Santana M, Seyit-Bremer G, Brignani S, Kaufmann R, Lowe E, Klein R, Seiradake E

Cell. 2020 Jan 9

doi: 10.1016/j.cell.2019.12.014.

Mutations in G Protein-Coupled Receptors: Mechanisms, Pathophysiology and Potential Therapeutic Approaches

Schöneberg T, Liebscher I

Pharmacol Rev. 2021 Jan

doi: 10.1124/pharmrev.120000011.

Arrestin-independent constitutive endocytosis of GPR125/ADGRA3

Spiess K, Bagger SO, Torz LJ, Jensen KHR, Walser AL, Kvam JM, Møgelmose AK, Daugvilaite V, Junnila RK, Hjortø GM, Rosenkilde MM

Ann N Y Acad Sci. 2019 Oct 29

doi: 10.1111/nyas.14263.

Training School on “Visualisation and Analysis of Structural Data"

20.03.2024–21.03.2024
University of Oxford, Oxford, UK

Organizer: Elena Seiradake (University of Oxford, UK)

Trainers:

• Prof. Elena Seiradake (Oxford, UK)
• Dr. Ed Lowe (University of Oxford, UK)
• Dr. Kamel el Omari (University of Oxford, UK)

Training School on “Cell-based assays to study Adhesion GPCR function"

28.06.2023–30.06.2023
Karolinska Institutet, Stockholm, Sweden

Organizers: Hannes Shihada, Lukas Grätz (Karolinska Institutet, Stockholm, Sweden)

Trainers:

• Prof. Ines Liebscher (Leipzig, DE)
• Prof. Evi Kostenis (Bonn, DE)
• Prof. Miriam Stoeber (Geneva, CH)
• Dr. Hannes Schihada (Marburg, DE)
• Dr. Lukas Grätz (Stockholm, SE)

Training School “Bioinformatics approaches in adhesion GPCR research”

07.09 2022–09.09.2022
University of Belgrade, Serbia

Organizers: Biljana Stankovic (Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, RS), Nikola Kotur (Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, RS), Milan Secanski (Vinča Institute of Nuclear Sciences, University of Belgrade, RS)

Trainers:

• Vladimir Jovanović (Berlin DE)
• Andrea Gelemanović (Split, HR)
• Dr. Teodora Đikić (Strasbourg, FR)

Structure-Function-Analyses of Adhesion GPCRs

Virtual Training School
2021-09-13 to 2021-09-14

Organizers: Laura Kilpatrick & Mark Soave (University of Nottingham, UK)

Trainers:

• Martin Gustavsson (KU, DK)
• Dimitry Veprintsev (UoN, UK)
• Eline Koers (UoN, UK)
• Gáspár Pándy-Szekeres (KU, DK)
• Jarkko Lackman (KU, DK)
• Albert Kooistra (KU, DK)

Animal models for Adhesion GPCR research

Virtual Training School
2020-10-05 to 2020-10-06

Organizer: Katarina Trajkovic (Mediterranean Institute for Life Sciences Split, HR)

Trainers:

• Jörg Hamann (Amsterdam University Medical Centers, Netherlands)
• Samantha Hughes (Hogeschool van Arnhem en Nijmegen, Netherlands)
• Hsi-Hsien Lin (Chang-Gung University College of Medicine, Taiwan)
• Kelly Monk (Oregon Health & Science University, USA)

Deliverable 1

Implementation of bioinformatic tools to provide tissue-specific expression analysis and variant analysis
(single nucleotide polymorphisms, mutations, splice variants)

Proof of progress with achieving the deliverable:

https://www.ernestbari21.eu/

https://doi.org/10.1093/nar/gkae145

Deliverable 2

New transcriptome data establishment including sample harvesting and preparation, sample sequencing and bioinformatical analysis (genome assembly, splice variant analysis, comparison between species with identification of conservation or new variants, genotype/phenotype associations)

Proof of progress with achieving the deliverable:

doi: 10.1016/j.matbio.2024.02.005

doi: 10.1016/j.bbrc.2021.12.006

doi: 10.3390/ijms222111803

doi: 10.3390/cells12151988

doi: 10.1038/s41366-020-0570-2

Deliverable 3

Structure studies including protein purification for crystal structures, NMR studies, antibody and nanobody production, spectroscopy studies (NMR, DEER), Crystal structures of functional domains and full-length receptors.

Proof of progress with achieving the deliverable:

doi: 10.1038/s41586-022-04619-y

doi: 10.1016/j.phrs.2023.106971

doi: 10.1016/j.cell.2019.12.014

Deliverable 4

Structure-function studies including analysis of receptor expression, mutagenesis and signal transduction of identified variants.

Proof of progress with achieving the deliverable:

doi: 10.1111/nyas.14263

doi: 10.3389/fcell.2022.873278

doi: 10.15252/embj.2021107915

doi: 10.3390/cells10123557

doi: 10.3390/cells12151988

doi: 10.3390/cells13100791

doi: 10.1111/bcpt.13873

doi: 10.3390/cells13100874

doi: 10.1038/s41392-024-01810-7

doi: 10.1111/bcpt.13873

doi: 10.1101/2021.09.13.460127

doi: 10.1016/j.jbc.2021.100798

doi: 10.1093/noajnl/vdaa053

doi: 10.1124/pharmrev.120.000011

Deliverable 5

Analysis of activation modes of aGPCRs (defining mechano-activation, ligand and small compound screens, agonist binding pocket identification, identification of signalling pathways and networks)

Proof of progress with achieving the deliverable:

doi: 10.1016/j.bbrc.2021.12.006

doi: 10.1111/nyas.14263

doi: 10.1101/2021.09.13.460127

doi: 10.3390/cells12111551

doi: 10.1002/pro.4614

doi: 10.1038/s41586-023-05802-5

doi: 10.3389/fcell.2022.873278

doi: 10.3390/molecules27103108

doi: 10.1152/ajpcell.00465.2021

doi. 10.1016/j.phrs.2023.106971

doi: 10.1021/acs.nanolett.3c01163

doi: 10.1111/bcpt.13923

doi: 10.1016/j.celrep.2023.112679

doi: 10.7554/eLife.69061

Deliverable 6

Predictive receptor modelling that should implement structural and functional data to provide information on the dynamic changes under activation. Docking models should provide hits for agonists and antagonists that will be tested in screening assays.

Proof of progress with achieving the deliverable:

doi: 10.1016/j.molcel.2020.12.042

doi: 10.3390/ijms24097788

doi: 10.1016/j.jbc.2023.105356

Deliverable 7

Evaluation of disease-relevant mutations including 1) mutant receptor cloning, expression and signal transduction analysis, 2) establishment of mutant animal models and 3) In-depth phenotyping of mutant animal models.

Proof of progress with achieving the deliverable:

doi: 10.1002/dvg.23417

doi: 10.1038/s41392-024-01810-7

Deliverable 8

Establishment of different disease models in mouse, C. elegans, D. melanogaster and D. rerio and analysis of differences in aGPCR expression, splice variants or mutations in tissues affected in disease model.

Proof of progress with achieving the deliverable:

doi: 10.1002/dvg.23417

doi: 10.1016/j.matbio.2024.02.005

doi: 10.1016/j.bbrc.2021.12.006

doi: 10.1016/j.celrep.2023

doi: 10.1038/s41586-023-05802-5

doi: 10.3390/cells13100874

doi: 10.7554/eLife.56738

doi: 10.1038/s41392-024-01810-7

Deliverable 9

Establishment of genetic signatures related to aGPCRs to establish as diagnostic tools.

Proof of progress with achieving the deliverable:

doi: 10.1111/bcpt.13873

Deliverable 10

Application of identified mechanical properties, agonists or antagonists to established disease models.

Proof of progress with achieving the deliverable:

doi: 10.1111/bcpt.13873

Deliverable 11

Antibody, nanobody and compound production and evaluation in vitro and in animal models.

Proof of progress with achieving the deliverable:

doi: 10.3390/cells10123557

doi: 10.1016/j.jbc.2022.101949

doi: 10.3389/fimmu.2018.02830

Deliverable 12

To launch and maintain a technology platform accessible to all aGPCR researchers containing information on technologies and expertise every member can provide to the network for shared use (e.g. whole-genome sequencers, high-throughput imaging platforms, sample databanks).

Proof of progress with achieving the deliverable:

See “News” section for novel technologies. Further, a technology database is available in the members area.

Deliverable 13

Providing information on the availability of novel techniques to study aGPCRs such as protocols online and development of novel tools/techniques.

Proof of progress with achieving the deliverable:

See “News” section for novel technologies.

Deliverable 14

Dissemination of findings and progress among scientists and stakeholders through an Action webpage.

Proof of progress with achieving the deliverable:

See “News” section.

Core Group Meeting

08.02.2024
Funchal, Madeira, PT

Core Group Meeting

04.09.2023
Porto, PT

Virtual Mobility Grant

2021-09-27 to 2021-10-31
Ligand screening network for aGPCR

Virtual Mobility Grant

2021-10-01 to 2021-10-31
Transfer of knowledge on the design and application of optical biosensors to study adhesion GPCR function

Virtual Mobility Grant

2021-09-27 - 2021-10-30
Accurate modeling of aGPCR using AlphaFold2

Virtual Mobility Grant

2021-09-27 to 2021-10-15
Library Screening of Potential Adhesion G Protein-Coupled Receptor (aGPCR) Ligands

Virtual Mobility Grant

2021-10-05 to 2021-10-31
Advancing the set up of an adhesion GPCR Technology Database - engaging and empowering the network

Virtual Mobility Grant

2021-10-15 to 2021-10-25
Exploring the effects of electronic cigarettes on the expression of adhesion GPCRs