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

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Publications of the doctoral students

The tight junction (TJ) connects neighbouring epithelial or endothelial cells and is the central element of barrier function, as it controls paracellular passage of solutes and water. Whether the TJ simply increases tightness or selectively mediates permeability varies greatly in different tissues and is determined by the TJ protein composition. There are two families of TJ proteins, the claudins and the TAMPs. So far, 27 claudins were discovered in mammalia.

The second family of TJ proteins are the TAMPs, comprising Occludin, Tricellulin and Marvel D3.

TJs underlie extensive extra- and intracellular signalling, but also regulate epithelial functions and cellular differentiation. Furthermore, numerous TJ proteins serve as receptors for certain pathogens.

Thus, TJ proteins are involved in the pathogenesis of numerous diseases. Alterations in TJ composition and architecture may e.g. cause unwanted leak flux or antigen passage and may thus maintain disease activity or even directly trigger disease onset.

Through the support by the former DFG Research Group FOR 721/1 and /2, Berlin has become a center of TJ research, which is characterized by a close integration of basic and clinical research.

In this environment, our Research Training Group "TJ-Train" is located. Its aim is to train PhD and MD students together. On the one hand, the MD students will be introduced to basic science, and on the other hand the PhD students will be brought into contact with clinical aspects and objectives.

Per cohort, 12 PhD and 12 MD students will be trained, PhDs for a period of 3 years, MDs for a period of 12 months. Thus, "TJ-Train" will not only qualify students for research and impart broad basic knowledge but will also particularly strengthen the transfer of knowledge between theoretical and clinical research and promote translational research approaches.

Through the participating researchers and their working groups, all doctoral students will have access to a very wide range of methods (including modern molecular biological and electrophysiological techniques, biophysical and bioinformatics methods, super-resolution light microscopy, next generation sequencing), that will be applied to the analysis of cell culture models, animal models and human biopsies.

Articles (and some original papers) for introduction into the field:

• Krug SM, Fromm M (2020) Special issue on 'The tight junction and its proteins – more than just a barrier'. Int. J. Mol. Sci. 21(13): 4612 (10 pages) [PubMed] [WebPage] [PDF]

• Meoli L, Günzel D (2020) Channel functions of claudins in the organization of biological systems. BBA - Biomembranes 1862(9): 183344 (18 pages) (°IF 3.5) [Part of Special Volume "The vertebrate epithelial apical junctional complex", Hervé JC ed.] [PubMed] [WebPage] [PDF] [Supplementary Fig. S1]

• Piontek J, Krug SM, Protze J, Krause G, Fromm M (2020) Molecular architecture and assembly of the tight junction backbone. BBA - Biomembranes 1862(7): 183279 (15 pages) (°IF 3.4) [Part of Special Volume "The vertebrate epithelial apical junctional complex", Hervé JC ed.] [PubMed] [WebPage] [PDF] [Supplement]

• Günzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol. Rev. 93(2): 525-569 [PubMed] [WebPage] [PDF]

• Günzel D, Fromm M (2012) Claudins and other tight junction proteins. Compreh. Physiol. (former Handbook of Physiology) 2(3): 1819-1852 [PubMed] [WebPage] [PDF]

• Günzel D (2017) Claudins: vital partners in trans- and paracellular transport coupling. Pflügers Arch. 469: 35-44 [PubMed] [WebPage] [PDF]

• Krause G, Protze J, Piontek J (2015) Assembly and function of claudins: Structure-function relationships based on homology models and crystal structures. Semin. Cell Devel. Biol. 42: 3-12 [PubMed] [WebPage] [PDF]

• Higashi T, Miller AL (2017) Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells. Mol. Biol. Cell 28: 2023-2034 [PubMed] [WebPage] [PDF]

• Barmeyer C, Fromm M, Schulzke JD (2017) Active and passive involvement of claudins in the pathophysiology of intestinal inflammatory diseases. Pflügers Arch. 469: 15-26  [PubMed] [WebPage] [PDF]

• Eichner M, Protze J, Piontek A, Krause G, Piontek J (2017) Targeting and alteration of tight junctions by bacteria and their virulence factors such as Clostridium perfringens enterotoxin. Pflügers Arch. 469: 77-90 [PubMed] [WebPage] [PDF]

• Krug SM, Schulzke JD, Fromm M (2014) Tight junction, selective permeability, and related diseases. Semin. Cell Devel. Biol. 36: 166-176 [PubMed] [WebPage] [PDF]

• Lehmann M, Gottschalk B, Puchkov D, Schmieder P, Schwagerus S, Hackenberger CPR, Haucke V, Schmoranzer J (2015) Multicolor caged dSTORM resolves the ultrastructure of synaptic vesicles in the brain. Angew. Chem. Int. Ed. 54: 13230–13235 [PubMed] [WebPage] [PDF]

• Christ A, Herzog K, Willnow TE (2016) LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease. Dev. Dyn. 245: 569-579 [PubMed] [WebPage] [PDF]

• Milatz S, Himmerkus N, Wulfmeyer VC, Drewell H, Mutig K, Hou J, Breiderhoff T, Müller D, Fromm M, Bleich M, Günzel D (2017) Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na⁺ and Mg²⁺ transport. Proc. Natl. Acad. Sci. USA 114(2): E219-E227 [PubMed] [WebPage] [PDF+Supplement. "Paper of the month" 03/2017 of the German Physiological Society

• Hariharan K, Kurtz A, Schmidt-Ott KM (2015) Assembling kidney tissues from cells: the long road from organoids to organs. Front. Cell. Dev. Biol. 3: 70. 5 [PubMed] [WebPage] [PDF]

• Schumann M, Siegmund B, Schulzke JD, Fromm M (2017) Celiac disease: role of the epithelial barrier. Cell. Mol. Gastroent. Hepatol. 3(2): 150-162 [PubMed] [WebPage] [PDF]

• Epple HJ, Zeitz M (2012) Intestinal mucosal barrier function in HIV infection. Ann. N.Y. Acad. Sci. 1258: 19-24 [PubMed] [WebPage] [PDF]