Introduction 2004 2007 2006 2002 2003 Adherens junctions The function of adherens junctions 1996 2+ 2+ 1977 Cadherins and catenins 2005 2006 2006 2003 2007 ctn ctn 1 2000 1999 2003 2007 2004 Fig. 1 2+ ctn 2+ Double arrows question mark  ctn ctn ctn 2004 ctn 2004 2003 2005 ctn 2001 ctn 2000 2006 2006 2005 2005 2005 2002 1997 2004 2001 2003 Nectins and afadin 2003 2001 2004 trans trans trans 2007 1997 1998 2000 1999 2005 2006 1999 2006 Trans 2004 2002 2005 2001 1999 1997 1 2002 2000 1999 2003 2004 1 2007 Tight junctions The function of TJs 2001 2001 2006 2006 2001 2 1998 2000 2006 2006 Fig. 2 Integral membrane proteins at tight junctions of epithelial and endothelial can be grouped into three classes based on their overall organizations. The first class is characterized by two extracellular loops, four transmembrane regions, and two cytoplasmic tails (occludin, claudins, tricellulin). The second class consists of Ig-SF members which all contain two Ig-like domains. The third class (contains only one member, CRB3) is characterized by a short extracellular domain (36 AA), a single transmembrane domain and a short cytoplasmic tail. In contrast to the other integral membrane proteins, the function of the extracellular domain of CRB3 is not clear  Integral membrane proteins at TJs 2 cis trans 2006 1998 2005 2005 2 1988 2004 2001 2000 2003 2001 2003 2003 2004 3 2001 2003 2007 2003 2001 2001 2001 2002 2005 2006 2003 2002 2002b 2004 3 2004 2003 2005 Fig. 3 Double arrows  Multiprotein complexes at TJs 1993 1986 3 2007 2003 3 The ZO protein complex 2005 4 1998 2002 1999 1999 1999 1999 4 2006 2004 2006 Fig. 4 2003 3 2004 2002 2007 Double arrows solid lines double arrows   broken lines  The CRB3–Pals1–PATJ complex Drosophila 2003 2001 Drosophila 2002 3 2002b 2002 2004 2005 2005 The PAR-3–aPKC–PAR-6 complex C.elegans 2000 C.elegans 1988 par 2007 2006 Drosophila 2001 3 2001 2001 2003 2000 2001 2005 2006 2002 2002 2000 2003 2002 2007 2001 2002 2001 2002 2002 2001 2002 2001 Regulation of membrane asymmetry and TJ formation by the PAR-3–aPKC–PAR-6 complex 5 1993 1996 1995 1993 5 Fig. 5 vertical bar  1996 1999 2001 2002 1995 2002 5 2002 1999 2001 2002 2003 2001 2004 2001 2002 2002 2001 2001 2007 2003 2004 2005 2002 2005 2005 2005 2002 1997 2004 2004 Drosphila 2003 Drosphila Regulation of TJ maintenance by the Rich1–Amot complex 2006 6 2001 2004 2006 2002 6 2+ 2006 Fig. 6 Double arrows solid lines arrows broken lines  2006 2000 2003 6 2002 2005 2007 6 Signaling from TJs 4 2003 2003 2000 2006 2000 2006 2006 2006 2004 2004 2003 ctn 2004 2004 2004 ctn 2005 A protein complex at the lateral membrane which regulates TJ formation: the Scribble–Discs Large–Lethal Giant Larvae complex 7 Drosophila 2004 scrib dlg lgl 2004 Drosophila 2001 2003 2003 Drosophila 2007 2003 2006 Drosophila 2002 2005 2+ 2007 2003 2003 7 2006 7 2003 2006 Fig. 7 Double arrows solid lines double arrows broken lines  Protein complexes at cell junctions and cancer 2001 2007 Drosophila dlg scrib lgl 2004 2007 2005 2006 8 2006 2007 Fig. 8 left panel right panel  2002 2002 2005 2005 2005 9 2002 2007 9 Fig. 9 Left panel Middle panel Right panel  Protein complexes as targets for pathogens 2004 2006 1998 2000 2003 2001 Helicobacter pylori H.pylori H.pylori 2003 2005 H.pylori 2002 2002 2003 2007 2004 2004 2007 2004 Conclusions and perspectives The last decade has witnessed a steady increase in the number of new proteins localized at cell–cell contacts of epithelial cells. The identification of claudins at TJs has strongly increased the understanding of the molecular basis of TJ function. The identification of cell polarity protein complexes like the PAR-3–aPKC–PAR-6 complex and the CRB3–Pals1–PATJ complex at TJs has added new aspects on the mechanisms underlying the development of TJs. The identification of the nectin–afadin system provided evidence for a second major adhesive system besides the cadherin–catenin system at AJs. It also became evident that TJs and AJs are signaling centers which are actively engaged in regulating proliferation and differentiation through feed-back mechanisms with the cytoskeleton and the nucleus. 2004 1999 2003 2004 1999 2002 2007 2002 2007 10 2005 2007 2007 2007 2006 Fig. 10 JXP MV PNL PNJ SLI  2004 2003 2006 2006 2006 1999 2003 3 4 2004 2003 2002a Drosophila 2003