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DFG Research Unit FOR 721/2 Molecular Structure and Function of the Tight Junction |
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Project Z |
Michael Fromm,
Prof. MD
Institute of Clinical Physiology,
Campus Benjamin Franklin,
Charité, Freie Universität and Humboldt-Universität, Berlin
Jörg-Dieter Schulzke, Prof. MD
Section Nutritional Medicine, Campus Benjamin Franklin,
Charité, Freie Universität and Humboldt-Universität, Berlin
Susanne M. Krug, PhD
Institute of Clinical Physiology,
Campus Benjamin Franklin,
Charité, Freie Universität und Humboldt-Universität, Berlin
Freeze fracture electron microscopy
and two-path impedance spectorscopy
In the Z-project, in addition to general administrative duties two techniques are implemented which were beneficial to all FOR projects.
The first is freeze-fracture electron microscopy (FFEM) and morphometric analysis of tight junction strands.
The second is two-path impedance spectroscopy (2PI). We have developed this technique (Krug et al., 2009, Biophys. J.) in order to measure separately transcellular and paracellular electrical resistances of epithelial structures. In this way ion conductivity can be directly associated with the cell membranes and / or the tight junctions.
Granted by project Z
Elisabeth Schultze, secretary
Anja Fromm, tech. assistant (50% by Project Z)
Coworker
In-Fah Lee, tech. assistant
Conrad MP*, Piontek J* (*shared first authorship), Günzel D, Fromm M, Krug SM (2016, online 2015) Molecular basis of claudin-17 anion selectivity. Cell. Mol. Life Sci. 73(1): 185-200 (IF 5.7) [PubMed] [WebPage] [PDF] [Supplement] TP1+TP6+TP7+TPZ{FFEM}
Dittmann I, Amasheh M, Krug SM, Markov AG, Fromm M, Amasheh S (2014) Laurate permeabilizes the paracellular pathway for small molecules in the intestinal epithelial cell model HT-29/B6 via opening the tight junctions by reversible relocation of claudin-5. Pharm. Res. 31(9): 2539–2548 {Erratum about Title misprint: Pharm. Res. 32(2): 737} (IF 3.4) [PubMed] [WebPage] [PDF] TP1+TP2+TPZ{2PI}
Hering NA*, Richter JF* (*shared first authorship), Fromm A, Wieser A, Hartmann S, Günzel D, Bücker R, Fromm M, Schulzke JD° (°corresponding author), Troeger H (2014) TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signalling in HT-29/B6 cells. Mucosal Immunol. 7(2): 369-378 (IF 7.0) [PubMed] [WebPage] [PDF] TP2+TP1+TP7+TPZ{2PI}
Zakrzewski SS, Richter JF, Krug SM, Jebautzke B, Lee IM, Rieger J, Sachtleben M, Bondzio A, Schulzke JD, Fromm M, Günzel D (2013) Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium. PLOS One 8(11): e79643 (print pages 1-12) (IF 3.7) [PubMed] [WebPage] [PDF] [Supplements] TP7+TP1+TP2+TPZ{2PI, FFEM}
Doerfel MJ, Westphal JK, Krug SM, Bellmann C, Blasig IE, Fromm M, Tauber R, Huber O (2013) CK2-dependent phosphorylation of occludin regulates the interaction with ZO-proteins and tight junction integrity. Cell Commun. Signal. 11(1): 40 (IF 5.5) [PubMed] [WebPage] [PDF] {2PI}
Kirschner N*, Rosenthal R* (*shared first authorship), Furuse M, Moll I, Fromm M, Brandner JM (2013) Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. J. Invest. Dermatol. 133(5): 1161-1169 (IF 6.3) [PubMed] [WebPage] [PDF] [Supplement] {2PI}
Günzel D, Fromm M (2012) Claudins and other tight junction proteins. Comprehensive Physiology (former Handbook of Physiology) 2(3): 1819-1852 [PubMed: soon] [WebPage] [PDF] {FFEM}
Günzel D, Zakrzewski S, Schmid T, Pangalos M, Wiedenhoeft J, Blasse C, Ozboda C, Krug SM (2012) From TER to trans- and paracellular resistance: Lessons from impedance spectroscopy. Ann. N.Y. Acad. Sci. 1257: 142-151 (IF 3.2) [PubMed] [WebPage] [PDF] (Review) {2PI}
Hackel D, Krug SM, Sauer RS, Mousa SA, Böcker A, Pflücke D, Wrede EJ, Kistner K, Hoffmann T, Niedermirtl B, Sommer C, Bloch L, Huber O, Blasig IE, Amasheh S, Reeh PW, Fromm M, Brack A, Rittner HL (2012) Transient opening of the perineurial barrier for analgesic drug delivery. Proc. Natl. Acad. Sci. USA 109(29): E2018-E2027 (IF 9.7) [PubMed] [WebPage] [PDF] {2PI}
Krug SM, Amasheh M, Dittmann I, Christoffel I, Fromm M, Amasheh S (2013, online 12.10.2012) Sodium caprate as an enhancer of macromolecule permeation across tricellular tight junctions of intestinal cells. Biomaterials 34(1): 275-282 (IF 7.4) [PubMed] [WebPage] [PDF] {2PI}
Krug SM, Günzel D, Conrad MP, Rosenthal R, Fromm A, Amasheh S, Schulzke JD, Fromm M (2012) Claudin-17 forms tight junction channels with distinct anion selectivity. Cell. Mol. Life Sci. 69(16): 2765-2778 (IF 6.6) [PubMed] [WebPage] [PDF] [Supplement]
Rosenthal R*, Günzel D* (*shared first authorship), Finger C, Krug SM, Richter JF, Schulzke JD, Fromm M, Amasheh S (2012) The effect of chitosan on transcellular and paracellular mechanisms in the intestinal epithelial barrier. Biomaterials 33(9): 2791-2800 (IF 7.9) [PubMed] [WebPage] [PDF] [Supplement]
Bücker R, Krug SM, Rosenthal R, Günzel D, Fromm A, Zeitz M, Chakraborty T, Fromm M, Epple HJ, Schulzke JD (2011) Aerolysin from Aeromonas hydrophila perturbs tight junction integrity and cell lesion repair in intestinal epithelial HT-29/B6 cells. J. Infect. Dis. 204 (8): 1283-1292 [PubMed] [WebPage] [PDF]
Hering NA, Richter JF, Krug SM, Günzel D, Fromm A, Bohn E, Rosenthal R, Bücker R, Fromm M, Troeger H, Schulzke JD (2011) Yersinia enterocolitica induces epithelial barrier dysfunction through regional tight junction changes in colonic HT-29/B6 cell monolayers. Lab. Invest. 91: 310-324 [PubMed] [WebPage] [PDF] [Supplement DOC]
Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD (2010) TNFa-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, pAkt, and NFkB signaling. J. Cell Sci. 123(23): 4145-4155 [PubMed] [WebPage] [PDF] [Supplements]
Günzel D, Krug SM, Rosenthal R, Fromm M (2010) Biophysical methods to study tight junction permeability. Curr. Top. Membr. 65: 39-78 [Directory] [WebPage] [PDF] (review / book chapter)
Milatz S, Krug SM, Rosenthal R, Günzel D, Müller D, Schulzke JD, Amasheh S*, Fromm M* (*shared last authorship) (2010) Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes. Biochim. Biophys. Acta Biomembr. 1798: 2048-2057 [PubMed] [WebPage] [PDF]
Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, Günzel D, Fromm M
(2010) Claudin-2, a component of the tight junction, forms a paracellular water channel. J. Cell Sci.
123(11): 1913-1921 [PubMed] [WebPage] [PDF]
[Supplement]
Award
Krug SM, Bojarski C, Fromm A, Schulzke JD, Fromm M (2010) The tight junction protein tricellulin in Crohn's disease and ulcerative colitis. Poster award of the European Intestinal Transport Group (EITG), Salerno, Italy
Publications 2007 - 2009 (FOR 721/1)
Amasheh S*, Milatz S* (*shared first authorship), Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem. Biophys. Res. Comm. 378(1): 45-50 [PubMed] [WebPage] [PDF] {2PI}
Fromm M, Krug SM, Zeissig S, Richter JF, Rosenthal R, Schulzke JD, Günzel D (2009) High resolution analysis of barrier function. Ann. N.Y. Acad. Sci. 1165: 74-81 [PubMed] [WebPage] [PDF] {2PI}
Krug SM, Amasheh S, Richter JF, Milatz S, Günzel D, Westphal JK, Huber O, Schulzke JD,
Fromm M (2009) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability.
Mol. Biol. Cell 20: 3713-3724 [PubMed] [WebPage] [PDF]
[Supplement text] [Supplement
video]
{FFEM, 2PI}
Krug SM, Fromm M, Günzel D (2009) Two-path impedance spectroscopy for measuring paracellular and transcellular epithelial resistance. Biophys. J. 97(8): 2202-2211 [PubMed] [WebPage] [PDF] [Supplement] {2PI}
Mankertz J*, Amasheh M*, Krug SM, Fromm A, Amasheh S, Hillenbrand B, Tavalali S, Fromm M, Schulzke JD (2009) TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tiss. Res. 336(1): 67-77 (*shared first authorship) [PubMed] [WebPage] [PDF] {2PI}
Schulzke JD*, Ploeger S* (*shared first authorship), Zeissig S, Amasheh M, Fromm A, Troeger H, Richter JF, Bojarski C, Schumann M, Fromm M (2009) Tight junctions in intestinal inflammation. Ann. N.Y. Acad. Sci. 1165: 294-300 [PubMed] [WebPage] [PDF] {FFEM}
Will C, Fromm M, Müller D (2008) Claudin tight junction proteins: novel aspects in paracellular transport. Periton. Dialysis Int. 28(6): 577-584 [PubMed] [PDF] {FFEM}
Zeissig S, Bürgel N, Günzel D, Richter JF, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin-2, -5 and -8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56(1): 61-72 [PubMed] [WebPage] [PDF] {FFEM}
Doctoral thesis
Krug SM (2009) Tricellulin und seine Funktion in der trizellulären Tight Junction von Epithelzellen. Dissertation, Biochemie, Freie Universität Berlin {FFEM, 2PI}
Previous work
Bentzel CJ, Fromm M, Palant CE, Hegel U (1987) Protamine alters structure and conductance of Necturus gallbladder tight junctions without major electrical effects on the apical cell membrane. J. Membr. Biol. 95: 9-20. [PubMed] [PDF]
Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD (1999a) Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 116: 301-309. [PubMed] [WebPage] [PDF]
Schmitz H, Fromm M, Bentzel CJ, Scholz P, Bode H, Epple HJ, Riecken EO, Schulzke JD (1999b) Tumor necrosis factor-alpha (TNFa) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J. Cell Sci. 112: 137-146. [PubMed] [PDF]
Schulzke JD, Bentzel CJ, Schulzke I, Riecken EO, Fromm M (1998) Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatric Res. 43: 435-441. [PubMed] [WebPage]
Schulzke JD, Fromm M, Bentzel CJ, Menge H, Riecken EO (1987) Adaptation of the jejunal mucosa in the experimental blind loop syndrome: changes in paracellular conductance and tight junction structure. Gut 28: 159-164. [PubMed] [PDF]
Schulzke JD, Fromm M, Bentzel CJ, Zeitz M, Menge H, Riecken EO (1992) Ion transport in the experimental short bowel syndrome of the rat: Increased glucose-dependent Na-absorption is the main adaptive response. Gastroenterology 102: 497-504. [PubMed] [PDF]
Schulzke JD, Fromm M, Riecken EO, Binder HJ, Hrsg. (2000) Epithelial transport and barrier function: pathomechanisms in gastrointestinal disorders. Ann. N.Y. Acad. Sci. 915: 1-375. [Contents & links to full papers]
Schulzke JD, Fromm M, Zeitz M, Menge H, Riecken EO, Bentzel CJ (1990) Tight junction regulation during impaired ion transport in blind loops of rat jejunum. Res. Exp. Med. 190: 59-68. [PubMed]