New aspects of the molecular constituents of tissue barriers
- 240 Downloads
Epithelial and endothelial tissue barriers are based on tight intercellular contacts (Tight Junctions, TJs) between neighbouring cells. TJs are multimeric complexes, located at the most apical border of the lateral membrane. So far, a plethora of proteins locating at tight intercellular contacts have been discovered, the role of which has just partly been unraveled. Yet, there is convincing evidence that many TJ proteins exert a dual role: They act as structural components at the junctional site and they are involved in signalling pathways leading to alterations of gene expression and cell behaviour (migration, proliferation). This review will shortly summarize the classical functions of TJs and TJ-related proteins and will introduce a new category, termed the “non-classical” functions of junctional proteins. A particular focus will be directed towards the nuclear targeting of junctional proteins and the downstream effects elicited by their intranuclear activities.
KeywordsTissue-barriers Epithelia Endothelia Tight junctions
This work was supported by the Austrian FWF P-18743 and by research grants from the Paracelsus Medical Private University (PMU) Salzburg, Austria. Bauer HC and Bauer H are participants of the NEUROBID consortium (EU 7th FP).
- Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005) High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307:1621–1625PubMedGoogle Scholar
- Bauer H, Zweimueller-Mayer J, Steinbacher P, Lametschwandtner A, Bauer HC (2010) The dual role of zonula occludens (ZO) proteins. J Biomed Biotechnol:402593Google Scholar
- Ben-Yosef T, Belyantseva IA, Saunders TL, Hughes ED, Kawamoto K, Van Itallie CM, Beyer LA, Halsey K, Gardner DJ, Wilcox ER, Rasmussen J, Anderson JM, Dolan DF, Forge A, Raphael Y, Camper SA, Friedman TB (2003) Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum Mol Genet 12(16):2049–2061Google Scholar
- Buchert M, Darido C, Lagerqvist E, Sedello A, Cazevieille C, Buchholz F, Bourgaux JF, Pannequin J, Joubert D, Hollande F (2009) The symplekin/ZONAB complex inhibits intestinal cell differentiation by the repression of AML1/Runx1. Gastroenterology. 137:156–64, 164 e1-3Google Scholar
- Buchert M, Papin M, Bonnans C, Darido C, Raye WS, Garambois V, Pelegrin A, Bourgaux JF, Pannequin J, Joubert D, Hollande F (2010) Symplekin promotes tumorigenicity by up-regulating claudin-2 expression. Proc Natl Acad Sci USA 107:2628–2633Google Scholar
- Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S, Vestweber D (2001) The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J 20:3738–3748Google Scholar
- Izumi Y, Hirose T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T, Tabuse Y, Kemphues KJ, Ohno S (1998) An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J Cell Biol 143:95–106PubMedGoogle Scholar
- Kawaguchi M, Hager HA, Wada A, Koyama T, Chang MS, Bader DM (2008) Identification of a novel intracellular interaction domain essential for Bves function. PLoS One 3:e2261Google Scholar
- Nakamura T, Blechman J, Tada S, Rozovskaia T, Itoyama T, Bullrich F, Mazo A, Croce CM, Geiger B, Canaani E (2000) huASH1 protein, a putative transcription factor encoded by a human homologue of the Drosophila ash1 gene, localizes to both nuclei and cell–cell tight junctions. Proc Natl Acad Sci USA 97:7284–7289PubMedGoogle Scholar
- Oku N, Sasabe E, Ueta E, Yamamoto T, Osaki T (2006) Tight junction protein claudin-1 enhances the invasive activity of oral squamous cell carcinoma cells by promoting cleavage of laminin-5 gamma2 chain via matrix metalloproteinase (MMP)-2 and membrane-type MMP-1. Cancer Res 66:5251–5257PubMedGoogle Scholar