Langenhan Lab

Adhesion G protein-coupled receptors

We are dedicated to solve important questions regarding this outstanding yet insufficiently understood receptor family:

• Which stimuli activate adhesion GPCRs?
• Which effects on cells, tissues and organs are controlled through adhesion GPCRs?
• How do defective adhesion GPCR signals contribute to human diseases (neuropsychiatric conditions, immune diseases, cancers)?​

Molecular processes of synaptic transmission

We investigate the action of genes and proteins that partake in synaptic transmission and information processing:

• How do synaptic proteins interact at such small local (in the sub-nanometer range) and temporal (in the millisecond range) scales?
• How does disease arise from defective molecular components of the synaptic machinery?

Adhesion G protein-coupled receptors

• Enzymology of autoproteolysis and signaling function of the GAIN domain in adhesion GPCRs (supported through CRC 1423; collaboration with Prof. N. Sträter)
• Dynamic modulation of adhesion GPCR function through complex formation (supported through CRC 1423; collaboration with Dr. N. Scholz)
• Functional analysis of the adhesion GPCR class in Drosophila (previously supported through FOR 2149; collaboration with Dr. N. Scholz)
• Interaction of adhesion GPCR signalling and ionotropic pathways during mechano-sensory signal transduction (previously supported through FOR 2149; collaboration with Prof. R.J. Kittel)
• FRET-based monitoring of Adhesion class G protein-coupled receptor activity (previously supported through CRC-TRR 166)
• Physiology and pathophysiology of mechanoceptive signalling pathways
• Disease models for neuropsychiatric conditions, immune system ailments and cancers
  

• Molecular control of the synaptic cleft dimensions
• Diseases models for neuropsychiatric conditions
  

Administration

• Bianca Löffler
  

Technical Assistance

• Christoph-Otto Naumann
• Frank Struck
• Katrin Michel​
• Lena Abicht
  
• Paula Beckmann
• Svenja Kapplinghaus
  

Scientific Team

• Anne-Kristin Dahse - PostDoc
• Berkay Demirbas - PhD candidate
• Elisabeth Triegel ​- MD candidate
• Fabian Pohl​ - PostDoc
• Lina Zielke ​- PhD candidate
  
• Marek Körner ​ - PhD candidate, jointly with the Scholz lab
  
• Max Buhlan - Student helper
  
• Nil Demir - PhD candidate
  
• Prabakaran Annadurai​ - PhD candidate
• Stephanie Häfner - PostDoc​
  
• Ume Aiman ​- PhD candidate, jointly with the Ljaschenko lab
  
• William Hamlet​ - PhD candidate
  

Cooperations

• AG Blanco-Redondo
  
• AG Ljaschenko
  
• AG Mrestani (Clinician Scientist group, in cooperation with the "Klinik und Poliklinik für Neurologie" at UKL, Prof. J. Claßen)​
  
• AG Scholz​
  

see also https://www.langenhan-lab.org/​

(* equal contribution, ^# correspondence)

Bormann A*, Körner MB*, Dahse AK*, Gläser MS, Irmer J, Lede V, Alenfelder J, Lehmann J, Hall DCN, Thane M, Schleyer M, Kostenis E, Schöneberg T, Bigl M, Langenhan T, Ljaschenko D^#, Scholz N^# (2025). Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function. Cell Rep., 44(1),115078.
DOI: 10.1016/j.celrep.2024.115078

Seufert F, Pérez-Hernández G, Pándy-Szekeres G, Guixà-González R, Langenhan T, Gloriam DE^#, Hildebrand PW^# (2025). Generic residue numbering of the GAIN domain of adhesion GPCRs. Nat. Commun., 16, 246.
DOI: 10.1038/s41467-024-55466-6

Körner MB^#, Velluva A, Bundalian L, Krohn K, Schön K, Schumann I, Kromp J, Thum AS, Garten A, Hentschel J, Jamra RA, Mrestani A, Scholz N, Langenhan T, Le Duc D^# (2025). Drosophila WDFY3/Bchs overexpression impairs neural function. J. Neurogenet., 1-16.
DOI: 10.1080/01677063.2025.2465536​

Langenhan T (2024). Modularization of adhesion G protein-coupled receptor (aGPCR) structure: how alternative splicing regulates synaptogenesis. Signal Transduct. Target. Ther., 9, 106.
DOI: 10.1038/s41392-024-01829-w​

Buhlan M, Ljaschenko D, Scholz N^#, Langenhan T^#​ (2024). Experimental modulation of physiological force application on leg joint neurons in intact Drosophila melanogaster. Nat. Protoc., 19, 113-126.​
DOI: 10.1038/s41596-023-00907-7

Vieira Contreras F​*, Auger GM*, Müller L, Richter V, Huetteroth W, Seufert F, Hildebrand PW, Scholz N, Thum AS, Ljaschenko D, Blanco-Redondo B^#, Langenhan T^# (2024). The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila. Cell Rep., 43, 113640.
DOI: 10.1016/j.celrep.2023.113640

Strutt H^#, Warrington S, Madathil ACK, Langenhan T, Strutt D^#​ (2023). Molecular symmetry breaking in the Frizzled-dependent planar polarity pathway. Curr. Biol., 33(24), 5340-5354.
DOI: 10.1016/j.cub.2023.10.071

Streit M*, Hemberger M*, Häfner S*, Knote F, Langenhan T^#, Beliu G# (2023). Optimized genetic code expansion technology for time-dependent induction of adhesion GPCR-ligand engagement. Protein Sci., 32, 4614.​
DOI: 10.1002/pro.4614

Seufert F*, Chung YK*, Hildebrand PW^#, Langenhan T^# (2023). 7TM domain structures of adhesion GPCRs: what’s new and what’s missing? Trends Biochem. Sci., 48(8), 726-739.
DOI: 10.1016/j.tibs.2023.05.007

Alexander SPH & CGTP Collaborators (2023). The concise guide to pharmacology 2023/24: G protein-coupled receptors. Br. J. Pharmacol., 180 Suppl 2, S23-S144.
DOI: 10.1111/bph.16177

Mrestani A*, Dannhäuser S*, Pauli M, Kollmannsberger P, Hübsch M, Morris L, Langenhan T, Heckmann M^#, Paul MM^# (2023). Nanoscaled RIM clustering at presynaptic active zones revealed by endogenous tagging. Life Sci. Alliance, 6(12), e202302021.
DOI: 10.26508/lsa.202302021​​

​Langenhan T (2023). Adhesion GPCRs in glioblastoma revisited. Cell Rep., 42(1), 113474.
DOI: 10.1016/j.celrep.2023.113474

Fu C, Huang W, Tang Q, Niu M, Guo S, Langenhan T, Song G^#, Yan J^# (2023). Unveiling Mechanical Activation: GAIN Domain Unfolding and Dissociation in Adhesion GPCRs. Nano Lett., ​23(20), 9179-9186.
DOI: 10.1021/acs.nanolett.3c01163

​Scholz N*^#, Dahse AK*, Kemkemer M, Bormann A, Auger GM, Vieira Contreras F, 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^# (2023). Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation. Nature, 615(7954), 945-953.
DOI: 10.1038/s41586-023-05802-5

Körner MB*, Velluva A*, Bundalian L, Radtke M, Lin CC, Zacher P, Bartolomaeus T, Kirstein AS, Mrestani A, Scholz N, Platzer K, Teichmann AC, Hentschel J, Langenhan T, Lemke JR, Garten A, Abou Jamra R^#, Le Duc D^# (2022). Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion. Sci. Rep., 12(1), 13507.
DOI: 10.1038/s41598-022-17604-2​

Paul MM*, Dannhäuser S*, Morris L*, Mrestani A*, Hübsch M, Gehring J, Hatzopoulos GN, Pauli M, Auger GM, Bornschein G, Scholz N, Ljaschenko D, Müller M, Sauer M, Schmidt H, Kittel RJ, DiAntonio A, Vakonakis I, Heckmann M^#, Langenhan T^# (2022). The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release. Brain, 145, 3787–3802.
DOI: 10.1093/brain/awac011

Götze KJ*, Mrestani A*, Beckmann P, Krohn K, Duc DL, Velluva A, Böhme MA, Heckmann M, Jamra RA, Lemke JR, Bläker H, Scholz N, Ljaschenko D^#, Langenhan T^# (2022). Improving one-step scarless genome editing in Drosophila melanogaster by combining ovoD co-CRISPR selection with sgRNA target site masking. Biol. Methods Protoc., 7, bpac003.
DOI: 10.1093/biomethods/bpac003

Beliu G*, Altrichter S*, Guixà-González R*, Hemberger M, Brauer I, Dahse A-K, Scholz N, Wieduwild R, Kuhlemann A, Batebi H, Seufert F, Pérez-Hernández G, Hildebrand PW^#, Sauer M^#, Langenhan T^# (2021). Tethered agonist exposure in intact adhesion/class B2 GPCRs through intrinsic structural flexibility of the GAIN domain. Mol. Cell, 81, 905-921.e5.
DOI: 10.1016/j.molcel.2020.12.042

Buettner JM*, Longang JKS*, Gerstner F, Apel KS, Blanco-Redondo B, Sowoidnich L, Janzen E, Langenhan T, Wirth B, Simon CM^# (2021). Central synaptopathy is the most conserved feature of motor circuit pathology across SMA mouse models. iScience,103376.
DOI: 10.1016/j.isci.2021.103376

Dannhäuser S*, Lux TJ*, Hu C, Selcho M, Chen JT-C, Ehmann N, Sachidanandan D, Stopp S, Pauls D, Pawlak M, Langenhan T, Soba P, Rittner HL^#, Kittel RJ^# (2020). Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination. eLife, 9, e56738.
DOI: 10.7554/eLife.56738

Mathiasen S, Palmisano T, Perry NA, Stoveken HM, Vizurraga A, McEwen DP, Okashah N, Langenhan T, Inoue A, Lambert NA, Tall GG, Javitch JA^# (2020). G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nat. Chem. Biol., 16, 1343–1350.
DOI: 10.1038/s41589-020-0617-7

Scholz N, Langenhan T^#, Schöneberg T^#(2019). Revisiting the classification of adhesion GPCRs. Ann. N. Y. Acad. Sci., 1456, 80–95.
DOI: 10.1111/nyas.14192

Blanco-Redondo B^#, Nuwal N, Kneitz S, Nuwal T, Halder P, Liu Y, Ehmann N, Scholz N, Mayer A, Kleber J, Kähne T, Schmitt D, Sadanandappa MK, Funk N, Albertova V, Helfrich-Förster C, Ramaswami M, Hasan G, Kittel RJ, Langenhan T, Gerber B, Buchner E^# (2019). Implications of the Sap47 null mutation for synapsin phosphorylation, longevity, climbing proficiency and behavioural plasticity in adult Drosophila. J. Exp. Biol., 222, jeb203505.​
DOI: 10.1242/jeb.203505

Langenhan T (2019). Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets. Basic Clin. Pharmacol. Toxicol., 126, 5–16.
DOI: 10.1111/bcpt.13223

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^# (2019). Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix. J. Cell Biol., 218, 1011–1026.
DOI: 10.1083/jcb.201806155

Blanco-Redondo B, Langenhan T^# (2018). Parallel Genomic Engineering of Two Drosophila Genes Using Orthogonal attB/attP Sites. G3: Genes Genomes Genet., 8, g3.200565.2018.
DOI: 10.1534/g3.118.200565

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^# (2017). Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons. eLife, 6, e28360.
DOI: 10.7554/eLife.28360

Scholz N^#, Monk KR, Kittel RJ, Langenhan T^# (2016). Adhesion GPCRs as a Putative Class of Metabotropic Mechanosensors. Handb. Exp. Pharmacol., 234, 221–247.​
DOI: 10.1007/978-3-319-41523-9_10

Backhaus P, Langenhan T, Neuser K^# (2016). Effects of transgenic expression of botulinum toxins in Drosophila. J. Neurogenet., 30, 22–31.
DOI: 10.3109/01677063.2016.1166223

Nieberler M, Kittel RJ, Petrenko AG, Lin HH^#, Langenhan T^#​ (2016). Control of Adhesion GPCR Function Through Proteolytic Processing. Handb. Exp. Pharmacol., 234, 83-109.
DOI: 10.1007/978-3-319-41523-9_5

Langenhan T^#, Piao X^#, Monk KR^#(2016). Adhesion G protein-coupled receptors in nervous system development and disease. Nat. Rev. Neurosci., 17(9), 550-61.
DOI: 10.1038/nrn.2016.86

​Hamann J*^#, Aust G*, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T*, Schiöth HB*^# (2015). International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors. Pharmacol. Rev., 67, 338–367.
DOI: 10.1124/pr.114.009647

Scholz N*, Gehring J*, Guan C*, Ljaschenko D, Fischer R, Lakshmanan V, Kittel RJ^#, Langenhan T^# (2015). The Adhesion GPCR Latrophilin/CIRL Shapes Mechanosensation. Cell Rep., 11, 866–874.
DOI: 10.1016/j.celrep.2015.04.008

Monk K, Hamann J, Langenhan T, Nijmeijer S, Schöneberg T, Liebscher I^# (2015). Adhesion GPCRs: From in vitro pharmacology to in vivo mechanisms. Mol. Pharmacol., 88(3), 617-23.
DOI: 10.1124/mol.115.098749​

​Langenhan T^#, Barr MM, Bruchas MR, Ewer J, Griffith LC, Maiellaro I, Taghert PH, White BH, Monk KR^# (2015). Model organisms in G protein–coupled receptor research. Mol. Pharmacol., 88(3), 596-603.
DOI: 10.1124/mol.115.098764

Liebscher I, Ackley B, Arac D, Ariestanti DM, Aust G, Bae B-I, Bista BR, Bridges JP, Duman JG, Engel FB, Giera S, Goffinet AM, Hall RA, Hamann J, Hartmann N, Lin, H-H, Liu M, Luo R, Mogha A, Monk KR, Peeters MC, Prömel S, Ressl S, Schiöth HB, Sigoillot SM, Song H, Talbot WS, Tall GG, White JP, Wolfrum U, Xu L, Piao X​^# (2014). New functions and signaling mechanisms for the class of adhesion G protein–coupled receptors. Ann. N. Y. Acad. Sci., 1333(1), 43-64.
DOI: 10.1111/nyas.12580

​Dawydow A*, Gueta R*, Ljaschenko D, Ullrich S, Hermann M, Ehmann N, Gao S, Fiala A, Langenhan T, Nagel G^#, Kittel RJ^# (2014). Channelrhodopsin-2-XXL, a powerful optogenetic tool for low-light applications. Proc. Natl. Acad. Sci. U.S.A., 111, 13972–13977.
DOI: 10.1073/pnas.1408269111

Langenhan T*^#, Aust G*, Hamann J* (2013). Sticky Signaling – Adhesion Class G Protein–Coupled Receptors Take the Stage. Sci. Signal., 6(276), re3.​
DOI: 10.1126/scisignal.2003825

Prömel S, Langenhan T^#, Araç D^# (2013). Matching structure with function: the GAIN domain of Adhesion-GPCR and PKD1-like proteins. Trends Pharmacol. Sci., 34, 470–478.
DOI: 10.1016/j.tips.2013.06.002

Prömel S, Aust G, Langenhan T, Schöneberg T^# (2013). Adhäsions-G-Protein-gekoppelte Rezeptoren – rätselhafte Riesen. Biospektrum, 19(7), 717-719.
DOI: 10.1007/s12268-013-0379-9

​Prömel S^#, Waller‐Evans H, Dixon J, Zahn D, Colledge WH, Doran J, Carlton MBL, Grosse J, Schöneberg T, Russ AP, Langenhan T^# (2012). Characterization and functional study of a cluster of four highly conserved orphan adhesion‐GPCR in mouse. Dev. Dyn., 241, 1591–1602.
DOI: 10.1002/dvdy.23841

Prömel S, Frickenhaus M, Hughes S, Mestek L, Staunton D, Woollard A, Vakonakis I, Schöneberg T, Schnabel R, Russ AP*, Langenhan T*^# (2012). The GPS Motif Is a Molecular Switch for Bimodal Activities of Adhesion Class G Protein-Coupled Receptors. Cell Rep., 2, 321–331.
DOI: 10.1016/j.celrep.2012.09.012

Araç D, Aust G, Calebiro D, Engel FB, Formstone C, Goffinet A, Hamann J, Kittel RJ, Liebscher I, Lin HH, Monk KR, Petrenko A, Piao X, Prömel S, Schiöth HB, Schwartz TW, Stacey M, Ushkaryov YA, Wobus M, Wolfrum U, Xu L, Langenhan T​^# (2012). Dissecting signaling and functions of adhesion G protein–coupled receptors. Ann. N. Y. Acad. Sci., 1276(1), 1-25.
DOI: 10.1111/j.1749-6632.2012.06820.x​

McGuinness L, Taylor C, Taylor RDT, Yau C, Langenhan T, Hart ML, Christian H, Tynan PW, Donnelly P, Emptage NJ^# (2010). Presynaptic NMDARs in the hippocampus facilitate transmitter release at theta frequency. Neuron, 68, 1109–1127.
DOI: 10.1016/j.neuron.2010.11.023

Waller-Evans H, Prömel S, Langenhan T, Dixon J, Zahn D, Colledge WH, Doran J, Carlton MBL, Davies B, Aparicio SAJR, Grosse J, Russ AP^# (2010). The Orphan Adhesion-GPCR GPR126 Is Required for Embryonic Development in the Mouse. PLoS One, 5(11), e14047.
DOI: 10.1371/journal.pone.0014047

Langenhan T^#, Russ AP^# (2010). Latrophilin signalling in tissue polarity and morphogenesis. Adv. Exp. Med. Biol., 706, 37-48.
DOI: 10.1007/978-1-4419-7913-1_3

Langenhan T, Prömel S, Mestek L, Esmaeili B, Waller-Evans H, Hennig C, Kohara Y, Avery L, Vakonakis I, Schnabel R, Russ AP^# (2009). Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev. Cell, 17, 494–504.
DOI: 10.1016/j.devcel.2009.08.008

Vakonakis I^#, Langenhan T, Prömel S, Russ A, Campbell ID (2008). Solution structure and sugar-binding mechanism of mouse latrophilin-1 RBL: a 7TM receptor-attached lectin-like domain. Structure, 16(6), 944-953.
DOI: 10.1016/j.str.2008.02.020

Langenhan T (2006). Ciliary neurotrophic factor (CNTF) in the olfactory system of rats and mice. Ann. Anat., 188(5), 411–413.
DOI: 10.1016/j.aanat.2006.05.008

Langenhan T, Sendtner M, Holtmann B, Carroll P, Asan E^# (2005). Ciliary neurotrophic factor-immunoreactivity in olfactory sensory neurons. Neuroscience, 134(4), 1179–1194.
DOI: 10.1016/j.neuroscience.2005.05.017

​Asan E^#, Langenhan T, Holtmann B, Bock H, Sendtner M, Carroll P (2003). Ciliary neurotrophic factor in the olfactory bulb of rats and mice. Neuroscience, 120(1), 99–112.
DOI: 10.1016/S0306-4522(03)00211-2