Discovering the Molecular Components of Intercellular Junctions--A Historical View

Abstract

The organization of metazoa is based on the formation of tissues and on tissue-typical functions and these in turn are based on cell -cell connecting structures. In vertebrates, four major forms of cell junctions have been classified and the molecular composition of which has been elucidated in the past three decades: Desmosomes, which connect epithelial and some other cell types, and the almost ubiquitous adherens junctions are based on closely cis-packed glycoproteins, cadherins, which are associated head-to-head with those of the hemi-junction domain of an adjacent cell, whereas their cytoplasmic regions assemble sizable plaques of special proteins anchoring cytoskeletal filaments. In contrast, the tight junctions (TJs) and gap junctions (GJs) are formed by tetraspan proteins (claudins and occludins, or connexins) arranged head-to-head as TJ seal bands or as paracrystalline connexin channels, allowing intercellular exchange of small molecules. The by and large parallel discoveries of the junction protein families are reported.

A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata

“…11 The mostly rather small, roundish-to-oval adherens junctions identified as the major myxoma cell-cell contacts represent typical mesenchymal structures, albeit with a special molecular composition. In these junctions, we have detected cadherin-11 as the only ubiquitous transmembrane glycoprotein, whereas additional N-cadherin was seen only in restricted regions of a few tumors, which we also take as an indication of the existence of two myxoma cell subtypes distinguished by their adherens junction composition, one with cadherin-11 only and the other containing both cadherin-11 and N-cadherin (for related observations, see Franke et al, 35 Franke, 36 Strumane et al, 37 Butany et al, 38 Reynen, 39 Pucci et al 40 and Burke et al 41 ). At present, however, we cannot rigorously exclude the alternative explanation that all myxoma adherens junctions may also contain some N-cadherin, which tends to be rapidly degraded by some of the proteolytic enzymes known to occur in tissue preparations from these tumors.…”

“…42 The molecular pattern of the adherens junction plaques of the cardiac myxomata is remarkably complex and specific. While most components identified, including a-and b-catenin, together with further armadillo proteins such as plakoglobin and proteins p120, p0071 and ARVCF, have also been found in other nonepithelial cells, 11,[35][36][37] it has been a surprise to find that the adherens junction plaques of all 32 myxomata examined contain an additional major armadillo protein, Pkp2, which so far has been considered to be a protein exclusive to desmosomes and to the composite junctions of cardiomyocytes. 12,17,35,43,44 As shown by Goossens et al, 45 the cardiomyocyte-specific plaque integration of Pkp2 is based on its binding to myocardial a-T-catenin, 45 a protein, however, that does not seem to be present in cardiac myxoma cells.…”

Ultrastructural Analysis Reveals cAMP-Dependent Enhancement of Microvascular Endothelial Barrier Functions via Rac1-Mediated Reorganization of Intercellular Junctions

“…Accordingly, in TER experiments, monolayers (MyEnd) responded to F/R treatment with a mildly increased resistance only, which further indi- Vol. 178,No. 5 cates that the intercellular contact zone reorganization is a morphological correlate for increased barrier functions.…”

Studies on cell junctions in an ex vivo human lung infection model

“…Gap junctions permit the transfer of ions [127], second messengers such as cAMP [128,129], siRNA [130] and small molecules with a molecular weight of up to 1 kDa enabling effective electrical and biochemical coupling between adjacent cells. Gap junctions are present in all tissue-forming cells [131] and are of particular importance in glial cells [132] and cardiomyocytes [133,134] rapidly forwarding action potentials. In this context, connecting cells with gap junctions provide both, increased speed in synaptic transmission and the ability to synchronize coupled cells for coordinated electrical and mechanical output enabling physiological processes such as muscle contraction [113].…”