Discovering the molecular components of intercellular junctions--a historical view.

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.