Discovering the molecular components of intercellular junctions

Discovering the Molecular Components of Intercellular Junctions—A Historical View
Werner W. Franke
Helmholtz Group for Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Correspondence: w.franke@dkfz.de

The organization of metazoa is based on the formation of tissues and on tissue-typical functions and these in turn are based on cell –cellconnecting 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 thehemi-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 ofsmall molecules. The by and large parallel discoveries of the junction protein families are reported.

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n the year of the bicenturial jubilee of Charles Darwin (born 1809) and his 1859 publication of the concept of natural selection as the decisive driving force of evolution, it is perhaps appropriate to begin this review with the notion that the four major kinds of cell – cell junctions areamong the oldest and most important structures contributing to the formation and functional diversification of multilayered metazoan organisms. From mere associations of individual cells, whether protozoan or parazoan, it was the cooperation of the molecular ensembles of these junctions to provide the basis for eumetazoan life. Note, however, that some protocadherin

glycoproteins andarmadillo-type proteins already occur in certain nonmetazoa (e.g., King et al. 2003; Nichols et al. 2006; for refs. Halbleib and Nelson 2006). In particular, diverse cell – cell junction molecules were— and are—needed to assemble and organize metazoan architecture, notably that of the Bilateria, to allow the formation of the epithelial layers of ectoderm and endoderm, mesodermderived tissues, and thesegregation of diverse kinds of interstitial cells and the organs derived therefrom. So, it is not so surprising that major kinds of cell junctional structures already exist in the lowest divisions of eumetazoa (e.g., Hobmayer et al. 1996, 2000).

Editors: W. James Nelson and Elaine Fuchs Additional Perspectives on Cell Junctions available at www.cshperspectives.org Copyright # 2009 Cold Spring HarborLaboratory Press; all rights reserved; doi: 10.1101/cshperspect.a003061 Cite this article as Cold Spring Harb Perspect Biol 2009;1:a003061

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W.W. Franke

In general, metazoan animals possess three intercellular junction systems of the adhering type formed by characteristic transmembrane molecules and proteins that assemble into specific submembranous plaques (Table 1). A fundamentallydifferent type, gap junctions, serves primarily as a system of assemblies of intercellular channels but also contributes to cell – cell adhesion. In summarizing the history of the discoveries of the molecular ensembles forming these junctions, it is striking that remarkably different arts of science and tribes

of cell biologists have contributed to the progress in this field. The intercellularjunctional systems are: (1) Desmosomes (maculae adherentes) are by far the most abundant junctions in stratified epithelia and have been studied with special impetus by researchers analyzing the cytoskeleton and tissue architecture, and by dermatologists. (2) Adherens junctions, including the zonulae and fasciae adherentes, have first attracted

Table 1. Constitutive molecular components of the major...