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

Project A4

Dr. Martin Lehmann     &   Prof. Dr. Volker Haucke 

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

High- and super-resolution imaging of tight junction component

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 different 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 anatomy 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 different TJ modulators, toxin exposition, hypoxia and inflammatory responses. Within the project we want to optimize super-resolution imaging (dSTORM, STED) for tissue and live-cell imaging and develop cell systems for super-resolution and live cell microscopy of TJ. Finally we want to perform quantitative analysis of the nanoscale TJ structure (strand discontinuities, branch points, internalization mechanisms) and composition of TJ in cells and tissues under pathological conditions. Specifically the nanoscale organisation of defined claudins, TAMPs , ZOs (i.e. pairs of Cldn1, -3, -4, -5, -18, ZO-1, occludin) will be investigated in tissue, primary cells and stable expression systems in endothelial and epithelial cell lines. Close collaborations with other basic and clinical research groups within TJTrain are planned. 

PhD doctoral student

  • Hannes Gonschior

Participation with project A4

Project-related publications

Note to TJ-Train students: If a paper is not accessible, please mail to  

  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.