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DFG Research Unit FOR 721/2 Molecular Structure and Function of the Tight Junction |
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Project 7 |
Dorothee Günzel, PhD
Institute of Clinical Physiology, Campus Benjamin Franklin, Charité Berlin
Renal claudins and their interactions
The aim of this project is firstly, the analysis of cis and trans interactions of kidney-typical claudins, and secondly, to clarify the interaction of claudin-16 with the apical chloride channel bestrophin. The experiments are performed on single and double transfected MDCK C7 cells and include the generation of claudin chimeras by exchanging the second extracellular loops, fluorescence studies of YFP-or CFP-tagged claudins, and freeze fracture electron microscopy analysis of tight junctions.
The interaction between claudin-16 with the two bestrophin isoforms 1 and 4 will be studied out by overexpression or knock-down (siRNA) of bestrophin in MDCK-C7 cells with or without claudin-16 coexpression. The functional effects of these interactions will be characterized and quantified electrophysiologically.
Granted by project 7
Dr. rer. nat. Susanne Milatz
2015
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 5.8) [PubMed] [WebPage] [PDF] [Supplement] TP1+TP6+TP7+TPZ{FFEM}
2014
Bücker R, Schulz E, Günzel D, Bojarski C, Lee IM, John LJ, Wiegand S, Janßen T, Wieler LH, Dobrindt U, Beutin L, Ewers C, Fromm M, Siegmund B, Troeger H, Schulzke JD (2014) α-Haemolysin of Escherichia coli: a potentiator of inflammatory activity in the colon. Gut 63(12): 1893-1901 (IF 14.7) [PubMed] [WebPage] [PDF] [Supplements] TP2+TP7+TP1
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}
Richter JF, Pieper R, Zakrzewski SS, Günzel D, Schulzke JD, Van Kessel AG (2014) Diets high in fermentable protein and fiber alter tight junction protein composition with minor effect on barrier function in piglet colon. Br. J. Nutr. 111(6): 1040-1049 (IF 3.3) [PubMed] [WebPage] [PDF] [Supplements] TP7+TP2
Rossa J, Plöger C, Vorreiter F, Saleh T, Protze J, Günzel D, Wolburg H, Krause G, Piontek J (2014) Claudin-3 and claudin-5 protein folding and assembly into the tight junction are controlled by non-conserved residues in transmembrane2 (TM3) and extracellular loop 2 (ECL2) segments. J. Biol. Chem. 289(11): 7641-7653 (IF 4.7) [29.01.14 Accepted] [PubMed] [WebPage] [PDF] [Supplements] TP6+TP7
Cording J, Berg J, Käding N, Bellmann C, Tscheik C, Westphal JK, Milatz S, Günzel D, Wolburg H, Piontek J, Huber O, Blasig IE (2013) Tight junctions: Claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate the claudin oligomerization. J. Cell Sci. 126: 554-564 (IF 6.1) [PubMed] [WebPage] [PDF] [Supplement] TP5+TP7+TP6+TP3
Schmid T, Bogdan M, Günzel D (2013) Discerning apical and basolateral properties of HT-29/B6 and IPEC-J2 cell layers by impedance spectroscopy, mathematical modeling and machine learning. PLOS One 8(7): e62913 (printed pages 1-12) (IF 3.5) [PubMed] [WebPage] [PDF] [Supplements, PDF] TP7
Schulzke JD, Siegmund B, Günzel D (2013) New insights in intestinal secretion. Gut ###: ###-### (IF 13.3) (Commentary) [PubMed] [WebPage] [PDF] TP2+TP7
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 3.5) [PubMed] [WebPage] [PDF] [Supplements] TP7+TP1+TP2+TPZ{2PI, FFEM}
Reviews
Günzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol. Rev. 93(2): 525-569 (IF 26.9) [PubMed] [WebPage] [PDF] TP7
2012
Kirschner N, Rosenthal R, Günzel D, Moll I, Brandner JM (2012) Tight junctions and differentiation – a chicken or the egg question? Exp. Dermatol. 21(3): 171-175 (IF 4.2) [PubMed] [WebPage] [PDF] TP9+TP1+TP7
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] TP1+TP7+TP2
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] TP1+TP7+TP2+TPZ
Schumann M, Günzel D, Buergel N, Richter JF, Troeger H, May C, Fromm A, Sorgenfrei D, Daum S, Bojarski C, Heyman M, Zeitz M, Fromm M, Schulzke JD (2012) Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in celiac disease. Gut 61(2): 220-228 (IF 10.1) [PubMed] [WebPage] [PDF] [Supplements] TP2+TP7+TP1
Reviews
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) TP7+TP1
Krug SM, Günzel D, Conrad MP, Lee IM, Amasheh S, Fromm M, Yu ASL (2012) Charge-selective claudin channels. Ann. N.Y. Acad. Sci. 1257: 20-28 (IF 3.2) [PubMed] [WebPage] [PDF] (Review) TP1+TP7
Plöger S, Stumpff F, Penner GB, Schulzke JD, Gäbel G, Martens H, Shen Z, Günzel D, Aschenbach JR (2012) Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann. N.Y. Acad. Sci. 1258: 52-59 (IF 3.2) [PubMed] [WebPage] [PDF] (Review) TP2+TP7
Schulzke JD, Günzel D, John LJ, Fromm M. Perspectives in tight junction research. Ann. N.Y. Acad. Sci. 1257: 1-19 (IF 3.2) [PubMed] [WebPage] [PDF] (Superinducing review) TP2+TP7+TP1
Handbook article
Günzel D, Fromm M (2012) Claudins and other tight junction proteins. Compreh. Physiol. (former Handbook of Physiology) 2(3): 1819-1852 [PubMed] [WebPage] [PDF] TP7+TP1
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] TP2+TP1+TP7+TPZ
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]
Nielsen HL, Nielsen H, Ejlertsen T, Engberg J, Günzel D, Zeitz M, Hering NA, Fromm M, Schulzke JD, Bücker R (2011) Oral and fecal Campylobacter concisus strains perturb barrier function by apoptosis induction in HT-29/B6 intestinal epithelial cells. PlosOne 6(8): e23858 (print pages 1-8) [PubMed] [WebPage] [PDF] TP2+TP7+TP1
Schulzke JD*, Andres S*, Amasheh M* (*shared first authorship), Fromm A, Günzel D (2011) Anti-diarrheal mechanism of the traditional remedy Uzara via reduction of active chloride secretion. PLoS One 6(3): e18107 (print 1-9) [PubMed] [WebPage] [PDF]
Stumpff F, Georgi MI, Mundhenk L, Rabbani I, Fromm M, Martens H, Günzel D (2011) Sheep rumen and omasum primary cultures and source epithelia: Barrier function aligns with expression of tight junction proteins. J. Exp. Biol. 214: 2871-2882 [PubMed] [WebPage] [PDF] [Supplement] TP7+TP1
2010
Amasheh S, Fromm M, Günzel D (2010) Claudins of intestine and nephron - a correlation of molecular tight junction structure and barrier function. Acta Physiol. 201(1): 133-140 [PubMed] [WebPage] [PDF] (Review) TP1+TP7
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)
Hillenbrand B, Günzel D, Richter JF, Höhne, Schreier E, Schulzke JD, Mankertz J (2010) Norovirus non-structural protein p20 leads to impaired restitution of epithelial defects by inhibition of actin cytoskeleton remodelling. Scand. J. Gastroent. 45(11):1307-1319 [PubMed] [WebPage] [PDF]
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]
Schmid T, Günzel D, Bogdan M (2010) Using an artificial neural network to determine electrical properties of epithelia. In: Diamantaras K, Duch W, Iliadis LS Eds., ICANN 2010, Part I, Lect. Notes Comput. Sci. 6352: 211-216 [26.07.10 In press]
Will C, Breiderhoff T, Thumfart J, Stuiver M, Kopplin K, Sommer K, Günzel D, Querfeld U, Meij IC, Shan Q, Bleich M, Willnow TE, Müller D (2010) Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting. Am. J. Physiol. Renal Physiol. [PubMed] [WebPage] [Full text preprint PDF]
Doctoral theses
Milatz S (2010) Functional characterization of the tight junction protein claudin-3 in epithelial and endothelial cells. Biology, Humboldt University Berlin. Dr. rer. nat., Magna cum laude
Haisch L (2010) Barrier function of claudins of the thick ascensing loop of Henles loop. Charité Berlin. Supervision: Müller D and Günzel D. Dr. med., Summa cum laude
Previous work
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]
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]
Günzel D, Amasheh S, Pfaffenbach S, Richter JF, Kausalya PJ, Hunziker W, Fromm M (2009) Claudin-16 affects transcellular Cl- secretion in MDCK cells. J. Physiol. (Lond.) 587(15): 3777-3793 [PubMed] [WebPage] [PDF] [Supplement]
Günzel D, Stuiver M, Kausalya PJ, Haisch L, Krug SM, Rosenthal R, Meij IC, Hunziker W, Fromm M, Müller D (2009) Claudin-10 exists in six alternatively spliced isoforms which exhibit distinct localization and function. J. Cell Sci. 122: 1507-1517 [PubMed] [WebPage] [PDF]
Yu ASL, Cheng MH, Angelow S, Günzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD (2009) Molecular basis for cation selectivity in claudin-2-based paracellular pores: Identification of an electrostatic interaction site. J. Gen. Physiol. 133(1):111-127 [PubMed] [WebPage] [PDF]
Amasheh S, Milatz S, Krug SM, Markov AG, Günzel D, Amasheh M, Fromm M (2009) Tight junction proteins as channel formers and barrier builders: claudin-2, -5, and -8. Ann. N.Y. Acad. Sci. 1165: 211-219 [PubMed] [WebPage] [PDF]
Günzel D, Haisch L, Pfaffenbach S, Krug SM, Milatz S, Amasheh S, Hunziker W, Müller D (2009) Claudin function in the thick ascending limb of Henle's loop. Ann. N.Y. Acad. Sci. 1165: 152-162 [PubMed] [WebPage] [PDF]
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]
Günzel D, Yu ASL (2009, Epub 16.09.2008) Function and regulation of claudins in the thick ascending limb of Henle. Pflügers Arch. 458(1): 77-88 [PubMed] [WebPage] [PDF]
Amasheh S*, Milatz S* (*shared first authorship), Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009, Epub 08.11.2008) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem. Biophys. Res. Comm. 378(1): 45-50 [PubMed] [WebPage] [PDF]
Troeger H *, Richter JF* (*shared first authorship), Beutin L, Günzel D, Dobrindt U, Epple HJ, Gitter AH, Zeitz M, Fromm M, Schulzke JD (2007) E. coli alpha-hemolysin induces focal leaks in colonic epithelium – a novel mechanism of bacterial translocation. Cell. Microbiol. 9(10): 2530-2540 [PubMed] [WebPage] [PDF]
Gabriel TE, Günzel D (2007) Quantification of Mg2+ extrusion and cytosolic Mg2+-buffering in Xenopus oocytes. Arch. Biochem. Biophys. 458(1): 3-15 [PubMed] [WebPage] [PDF]
Markov AG, Veshnyakova A, Krug S, Milatz S (2007) Expression of tight junction proteins in the epithelium of small intestine of the rat. Russ. J. Physiol. (Ross. Fiziol. Zh. Im. I. M. Sechenova) 93(9): 1043-1054 [PubMed]
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]