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

• Lena Abicht​ (Technician)
• Genevieve Auger (PhD Student)
• Paula Beckmann (Technician)
• Max Buhlan (MD Student)
• Alex Chung (PhD Student)
• Stephanie Häfner (PhD)
  
• Kerstin Heise (Technician)
• Marguerite Kemkemer
• Marek Körner (PhD Student)
• Bianca Löffler (Office Assistence)
• Amelie Meyer-Mölck (MD Student)
• Franz Müller (MD Student)
  
• Fabian Pohl​ (PhD)
• Frank Struck (Technician)​
• Elisabeth Triegel​ (MD Student)

Cooperation with Mrestani group (Clinician Scientist Group, in cooperation with the Department of Neurology/University hospital Leipzig, Prof. J. Claßen)

Cooperation with Blanco-Redondo group​

Cooperation with Ljaschenko group

Cooperation with Scholz group

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

(* equal contribution, ^# correspondence)

Adhesion G protein-coupled receptors

(selection)

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. 

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.

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. 

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.​

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. Molecular Cell 81:905-921.e5.

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

Langenhan T^#, Piao X^#, Monk KR^# (2016) Adhesion G protein-coupled receptors in nervous system development and disease. Nature Reviews Neuroscience 17:550–561.

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 Reports 11:866–874.

Langenhan T*^,#, Aust G*, Hamann J* (2013) Sticky Signaling—Adhesion Class G Protein–Coupled Receptors Take the Stage. Science Signaling 6:re3–re3.

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 Reports 2:321–331

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. Developmental Cell 17:494–504.

(additional 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 (2020) G12/13 is activated by acute tethered agonist exposure in the adhesion GPCR ADGRL3. Nature Chemical Biology 16:1343–1350.

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.

Scholz N, Langenhan T^#, Schöneberg T^# (2019) Revisiting the classification of adhesion GPCRs. Annals of the New York Academy of Sciences 1456:80–95.

Langenhan T (2019) Adhesion G protein–coupled receptors—Candidate metabotropic mechanosensors and novel drug targets. Basic & Clinical Pharmacology & Toxicology 126:5–16.

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

Nieberler M, Kittel RJ, Petrenko AG, Lin H-H^#, Langenhan T^# (2016) Adhesion G Protein-coupled Receptors, Molecular, Physiological and Pharmacological Principles in Health and Disease. Handbook of Experimental Pharmacology 234:83–109.

Scholz N^#, Monk KR, Kittel RJ, Langenhan T^# (2016) Adhesion GPCRs as a Putative Class of Metabotropic Mechanosensors. Handbook of Experimental Pharmacology 234:221–247.

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. Pharmacological Reviews 67:338–367.

Prömel S, Langenhan T^#, Araç D^# (2013) Matching structure with function: the GAIN domain of Adhesion-GPCR and PKD1-like proteins. Trends Pharmacological Sciences 34:470–478.

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. Developmental Dynamics 241:1591–1602.

Molecular processes of synaptic transmission

(selection)

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.

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. Biology Methods & Protocols 7:bpac003.

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. Journal of Cell Biology 218:1011–1026.

Additional publications

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.

Körner MB*, Velluva A*, Bundalian L, Radtke M, Lin C-C, Zacher P, Bartolomaeus T, Kirstein AS, Mrestani A, Scholz N, Platzer K, Teichmann A-C, Hentschel J, Langenhan T, Lemke JR, Garten A, Jamra RA^#, Duc DL^# (2022) Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion. Scientific Reports 12:13507.

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. Journal of Experimental Biology 222:jeb203505.

Backhaus P, Langenhan T, Neuser K (2016) Effects of transgenic expression of botulinum toxins in Drosophila. Journal of Neurogenetics 30:22–31.

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. Proceedings of the National Academy of Sciences of the United States of America 111:13972–13977.

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.