DFG Research Training Group "TJ-Train" (GRK 2318/2)
 Tight junctions and their proteins
Molecular features and actions in health and disease

Project A4     1st period    2nd period

Dr. Martin Lehmann     &   Prof. Dr. Volker Haucke 

Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP),
Berlin-Buch

Dynamic super-resolution imaging of tight junction components, lipids and Ions

The tight junction (TJ) connects neighboring epithelial or endothelial cells and acts as a barrier for solutes, water and pathogens. The TJ protein composition in tissues controls tightness and permeability and is regulated by dynamic protein assemblies, signaling and endocytosis.

The central aim of project A4 is to resolve the nanoscale molecular organization of TJs using super-resolution light microcopy and advanced live cell imaging under physiological and pathological conditions. We hypothesize that the nanoscale TJ strand composition and structure is changed by claudin/TAMP composition, toxin exposition, hypoxia and inflammatory responses. In order to understand organization principles and function of different TJ components we will combine STED microscopy with 50 nm resolution, FRET, FLIM, automated confocal microscopy and novel lipid/Ion flux assays with quantitative image analysis. Specifically the dynamic nanoscale organization of all claudins, occludin, ZOs and selected pairs of claudins/occludin will be investigated in tissues, primary cells and CrispR knock-in and knock-out epithelial cell lines. All results will be used to understand disease, knockout phenotypes, pathological conditions and inspire new pharmacological treatments. Close collaborations with other basic and clinical research groups within TJ-Train are planned.

3rd cohort PhD doctoral student

Roman Shobik

2nd cohort PhD doctoral student

Rozemarijn van der Veen
18.09.2024: Doctoral examination passed, "Regulation of claudin polymerization through intrinsic and extrinsic factors"

  • Martínez-Perafán F, Fromm A, van der Veen RE, Waldow A, Lehmann M, Krug SM, Günzel D, Rosenthal R, Fromm M, Piontek J (2025) Effect of claudin-1 or -3 expression on cation and water channel properties of claudin-2. BBA - Mol. Cell Res. 1872(4): 119930 (17 pages). doi: 10.1016/j.bbamcr.2025.119930 (°IF 4.6)

  • Schmied C, Ebner M, Samsó P, van der Veen R, Haucke V, Lehmann M (2024) OrgaMapper: a robust and easy-to-use workflow for analyzing organelle positioning. BMC Biol. 22(1): 220. doi: 10.1186/s12915-024-02015-8 (°IF 4.4)

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  • van der Veen RE, Piontek J, Bieck M, Saiti A, Gonschior H, Lehmann M (2024) Claudin-4 polymerizes after a small extracellular claudin-3-like substitution. J. Biol. Chem. 300(10): 107693 (14 pages). doi: 10.1016/j.jbc.2024.107693

    • (°IF 4.0)

  • Mukenhirn M, Wang CH, Guyomar T, Bovyn MJ, Staddon MF, van der Veen RE, Maraspini R, Lu L, Martin-Lemaitre C, Sano M, Lehmann M, Hiraiwa T, Riveline D, Honigmann A (2024) Tight junctions control lumen morphology via hydrostatic pressure and junctional tension. Dev. Cell 59(21): 2866-2881.e8. doi: 10.1016/j.devcel.2024.07.016 (°IF 10.7)

  • Gonschior H, Schmied C, van der Veen RE, Eichhorst J, Himmerkus N, Piontek J, Günzel D, Bleich M, Furuse M, Haucke V, Lehmann M (2022) Nanoscale segregation of channel and barrier claudins enables paracellular ion flux. Nat. Commun. 13(1): 4985 (20 pages). doi: 10.1038/s41467-022-32533-4, Supplement (IF 16.6)

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1st cohort PhD doctoral student

Hannes Gonschior
09.03.2023: Doctoral examination passed, "Nanoscale segregation of claudin-10a, -10b and -15 enables paracellular ion permeability"

  • van der Veen RE, Piontek J, Bieck M, Saiti A, Gonschior H, Lehmann M (2024) Claudin-4 polymerizes after a small extracellular claudin-3-like substitution. J. Biol. Chem. 300(10): 107693 (14 pages). https://doi.org/10.1016/j.jbc.2024.107693

    • (°IF 4.0)

  • Mecklenburg N*, Kowalczyk I*, Witte F* (*shared first authorship), Goerne J, Laier A, Mamo TM, Gonschior H, Lehmann M, Richter M, Sporbert A, Purfuerst B, Hübner N, Hammes A (2021) Identification of novel disease relevant modulators of the SHH pathway in the developing brain. Development 148(17): (17 pages) doi: 10.1242/dev.199307 (IF 6.9)

  • Gonschior H, Haucke V, Lehmann M (2020) Super-resolution imaging of tight and adherens junctions: Challenges and open questions. Int. J. Mol. Sci. 21(3): 744 (15 pages) [PubMed] [WebPage] [PDF] (Review) (IF 5.9)

  • Gonschior H, Schmied C, Van der Veen R, Eichhorst J, Himmerkus N, Piontek J, Günzel D, Bleich M, Furuse M, Haucke V, Lehmann M (2022) Nanoscale segregation of channel and barrier claudins enables paracellular ion flux. Nat. Commun. 13(1): 4985 (20 pages). doi: 10.1038/s41467-022-32533-4, Supplement (IF 16.6)

Participation with project A4

Priv.-Doz. Dr. Jörg Piontek
 

Project-related publications 

  1. Ketel K, Krauss M, Nicot AS, Puchkov D, Wieffer M, Müller R, Subramanian D, Schultz C, Laporte J, Haucke V (2016) A phosphoinositide conversion mechanism for exit from endosomes. Nature 529: 408-412

  2. Gimber N, Tadeus G, Maritzen T, Schmoranzer J, Haucke V (2015) Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins. Nature Commun. 6: 8392 (printed pages: 11)

  3. Koo SY, Kochlamazashvili G, Rost B, Puchkov D, Gimber N, Lehmann M, Tadeus G, Schmoranzer J, Rosenmund C, Haucke V*, Maritzen T* (*co-corresponding authors) (2015) Vesicular synaptobrevin/VAMP2 levels guarded by AP180 control efficient neurotransmission. Neuron 88: 330-344

  4. Lehmann M, Gottschalk B, Puchkov D, Schmieder P, Schwagerus S, Hackenberger CP, Haucke V, Schmoranzer J (2015) Multicolor 'caged' dSTORM resolves the ultrastructure of synaptic vesicles in the brain. Angew. Chem. 54: 13230-13235

  5. Seifert W, Kühnisch J, Maritzen T, Lommatzsch S, Hennies HC, Bachmann S, Horn D, Haucke V (2015) Cohen syndrome-associated protein COH1 physically and functionally interacts with the small GTPase RAB6 at the Golgi complex and directs neurite outgrowth. J. Biol. Chem. 290: 3349-3358

  6. Podufall J, Tian R, Knoche E, Puchkov D, Walter AM, Rosa S, Quentin C, Vukoja A, Jung N, Lampe A, Wichmann C, Böhme M, Depner H, Zhang YQ, Schmoranzer J, Sigrist SJ, Haucke V (2014) A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling. Cell Rep. 7: 1417-1425

  7. Wilhelm BG, Mandad S, Truckenbrodt S, Kröhnert K, Schäfer C, Rammner B, Koo SJ, Claßen GA, Krauss M, Haucke V, Urlaub H, Rizzoli SO (2014) Composition of synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344: 1023-1028

  8. Posor Y, Eichhorn-Grünig M, Puchkov D, Schöneberg J, Ullrich A, Lampe A, Müller R, Zar-bakhsh S, Gulluni F, Hirsch E, Krauss M, Schultz C, Schmoranzer J, Noé F, Haucke V (2013) Spatiotemporal control of endocytosis by phosphatidylinositol 3,4-bisphosphate. Nature 499: 233-237

  9. Lampe A, Haucke V, Sigrist SJ, Heilemann M, Schmoranzer J (2012) Multi-colour direct STORM with red emitting carbocyanines. Biol. Cell 104: 229-237

  10. Maritzen T, Zech T, Schmidt MR, Krause E, Machesky LM, Haucke V (2012) Gadkin negatively regulates cell spreading and motility via sequestration of the actin-nucleating ARP2/3 complex. Proc. Natl. Acad. Sci. USA 109: 10382-10387

The listed publications are relevant with respect to the technologies (i.e. super-resolution imaging) and cell systems applied, not the specific biological questions addressed.