9.B.41 The Occludin (Occludin) Family

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 compositions of them have been elucidated (Franke, 2009). 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. Their cytoplasmic regions assemble sizable plaques of special proteins anchoring cytoskeletal filaments. Tight junctions (TJs) and gap junctions (GJs) are formed by tetraspan proteins (claudins and occludins, or connexins and innexins, respectively). They are arranged head-to-head as TJ seal bands or as paracrystalline connexin/innexin channels, allowing intercellular exchange of small molecules. The parallel discoveries of the four types of junctional protein families are described by Franke (2009) from a historical standpoint.

Occludins are constituents of tight junctions in animals and are unique markers of these structures. They are present in polarized endothelial and epithelial tissue barriers. Occludin is able to oligomerize and form tight junction strands by homologous and heterologous interactions, but it has no direct tightening function. They have been implicated in mediating the Leak Pathway of epithelial cells (Monaco et al. 2021). Its oligomerization is affected by pro- and antioxidative agents or processes. Phosphorylation of occludin has been described at multiple sites and is proposed to play a regulatory role in tight junction assembly and maintenance and, hence, to influence tissue barrier characteristics. Redox-dependent signal transduction mechanisms are among the pathways modulating occludin phosphorylation and function. Blasig et al. (2011) discussed the concept that occludin plays a key role in the redox regulation of tight junctions, which has a major impact in pathologies related to oxidative stress and corresponding pharmacologic interventions. The MARVEL transmembrane motif of occludin has been shown to mediate oligomerization and targeting of the protein to the basolateral surface in epithelia (Yaffe et al., 2012). Tetrandrine, a bisbenzyl isoquinoline alkaloid, attenuates intestinal epithelial barrier defects caused by colitis through promoting the expression of occludin (Chu et al. 2021).

No transport function is recognized for occludins, but a occludin/ZO-1 complex regulates the barrier function of tight junctions (Tash et al. 2012). These proteins are believed to form a superfamily together with claudins (1.H.1), connexins (1.A.24) and innexins (1.A.25) as well as others for a total of 15 families within the Tetraspan (4 TMS) Junctional Complex (4JC) Superfamily. (Chou et al. 2017). 

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