Project B06 – Dynamic modulation of adhesion GPCR function through complex formation

The activity profile and signaling capacity of adhesion GPCRs (aGPCR) may be modulated through crosstalk between different cell surface molecules and may be triggered and/or modulated by mechanical input. We will identify ligand-receptor complexes of aGPCRs through in vitro and in vivo orthogonal labeling and photo-crosslinking as well as intermolecular FRET approaches, respectively. In a further tier of experiments, we will investigate if putative interactors affect aGPCR signaling in a mechano-dependent fashion, test if mechanical stimuli serve as a switch for aGPCR dimerization/oligomerization and investigate how the viscoelastic properties of these interactions correlate with aGPCR activity.

Contact

Prof. Dr. Tobias Langenhan, D.Phil. (Oxon) (Project Leader)

Leipzig University, Faculty of Medicine
Rudolf Schönheimer Institute of Biochemistry
Johannisallee 30, D-04103 Leipzig

Phone +49 341 97 22101
E-Mail
Web www.langenhan-lab.org/

Resources

  • in vitro and in vivo orthogonal labeling and photo-crosslinking as well as intermolecular FRET approaches

Publications

Mathiasen S, Palmisano T, Perry NA, Stoveken HM, Vizurraga A, McEwen DP, Okashah N, Langenhan T, Inoue A, Lambert NA, Tall GG, Javitch JA. G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nat Chem Biol. 2020 Aug 10. doi: 10.1038/s41589-020-0617-7. Epub ahead of print. Erratum in: Nat Chem Biol. 2020 Aug 17;: PMID: 32778842. [publisher correction: doi: 10.1038/s41589-020-0649-z]

Scholz NLangenhan T, Schöneberg T. Revisiting the classification of adhesion GPCRs. Ann N Y Acad Sci. 2019; 1456: 80-95.

Langenhan T*, Aust G*, Hamann J*. Sticky Signaling-Adhesion Class G Protein-Coupled Receptors Take the Stage. Sci Signal. 2013; 6:re3.

Langenhan T, Prömel S, Mestek L, Esmaeili B, Waller-Evans H, Hennig C, Kohara Y, Avery L, Vakonakis I, Schnabel R, Russ AP. Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev Cell. 2009; 17:494-504.

Scholz N. Cancer Cell Mechanics: Adhesion G Protein-coupled Receptors in Action? Front Oncol. 2018;

Langenhan T#, Piao X#, Monk KR#. Adhesion G protein-coupled receptors in nervous system development and disease. Nat Rev Neurosci. 2016; 17:550-61.

Prömel S#, Waller-Evans H, Dixon J, Zahn D, Colledge WH, Doran J, Carlton MBL, Grosse J, Schöneberg T, Russ AP, Langenhan T#. Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev Dyn. 2012b; 241:1591-602.

Scholz N#, Monk KR, Kittel RJ, Langenhan T#. Adhesion GPCRs as a Putative Class of Metabotropic Mechanosensors. Handb Exp Pharmacol. 234:221-47.

Scholz N*, Gehring J*, Guan C*, Ljaschenko D, Fischer R, Lakshmanan V, Kittel RJ#, Langenhan T#. The Adhesion GPCR Latrophilin/CIRL Shapes Mechanosensation. Cell Rep. 2015; 11:866-74.

Scholz N*, Guan C*, Nieberler M*, Grotemeyer A*, Maiellaro I, Gao S, Beck S, Pawlak M, Sauer M, Asan E, Rothemund S, Winkler J, Prömel S, Nagel G, Langenhan T#, Kittel RJ#. Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons. 2017; 6:e28360.

Prömel S, Frickenhaus M, Hughes S, Mestek L, Staunton D, Woollard A, Vakonakis I, Schöneberg T, Schnabel R, Russ AP, Langenhan T. The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors. Cell Rep. 2012; 2:321-31.

Scholz N*, Ehmann N*, Sachidanandan D, Imig C, Cooper BH, Jahn O, Reim K, Brose N, Meyer J, Lamberty M, Altrichter S, Bormann A, Hallermann S, Pauli M, Heckmann M, Stigloher C, Langenhan T#, Kittel RJ#. Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix. J Cell Biol. 2019; 218:1011-26.