![](images/logo_grk2318_s.jpg)
DFG Research Training Group "TJ-Train" (GRK 2318/1)
Tight junctions and their proteins
Molecular features and actions in health and disease
Project
A4
2nd
period
Dr.
Martin Lehmann
& Prof. Dr.
Volker Haucke
![](../images/brief1.gif)
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.
1st cohort PhD doctoral student
Hannes Gonschior
![](../images/brief1.gif)
-
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
48(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
Project-related publications
If
a paper is not accessible, please mail to
.
-
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
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)
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
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
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
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
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
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
Lampe A, Haucke V, Sigrist SJ, Heilemann M, Schmoranzer J (2012) Multi-colour direct STORM with red emitting carbocyanines.
Biol. Cell
104: 229-237
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.
|