Occludin Protein Family: Oxidative Stress and Reducing Conditions

Abstract

The occludin-like proteins belong to a family of tetraspan transmembrane proteins carrying a marvel domain. The intrinsic function of the occludin family is not yet clear. Occludin is a unique marker of any tight junction and is found in polarized endothelial and epithelial tissue barriers, at least in the adult vertebrate organism. Occludin is able to oligomerize and to form tight junction strands by homologous and heterologous interactions, but has no direct tightening function. 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. This review discusses the novel 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.

In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization

“…Due to the homology of the marvel domain of the TAMPs and the great variation in the length of their cytosolic tails a heterophilic interaction between the transmembrane domains of all three members has been assumed (Blasig et al, 2011;Westphal et al, 2010). As a matter of fact, Md3 is interacting with both Occl and Tric, at bicellular cell-cell contacts within one plasma membrane (cis-interaction).…”

“…However, interactions between the homologous marvel domains is unlikely as Occl and Tric are unable to associate heterophilically in the cell contact. Occl and Tric share a homologous coiled-coil and ELL-domain, respectively, which is absent in Md3 (Blasig et al, 2011). Md3 has only an extended N-terminal tail and nearly no C-terminal tail in the cytosol as an intracellular interaction site for cytosolic cisbinding domains of Occl and Tric.…”

“…Marchiando et al found that Occl is involved in the maintenance of the barrier function in vivo . Occl derived peptides may disrupt TJ formation (reviewed by Blasig et al, 2011). Furthermore, it is suggested that Occl is trans-interacting via its extracellular loops (for review see Blasig et al, 2011).…”

Tempol modulates changes in xenobiotic permeability and occludin oligomeric assemblies at the blood-brain barrier during inflammatory pain

“…Occludin is specifically localized to the TJ at endothelial cell margins (18,21) and links with the cytoskeleton through interactions with accessory proteins [i.e., zonulae occluden (ZO)-1, -2, and -3; Refs. 4,10]. It was previously suggested that while occludin is localized to the TJ, it is not essential for TJ assembly and has no direct "tightening" function (4).…”

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

“…The investigated cell junctions, except for ZO-1, are transmembrane proteins with two extracellular loops that are accessible to nucleophilic attacks. Therefore, hydrogen peroxide could oxidize redox sensitive cell junctions directly or may influence different redox sensitive signal transduction pathways that modify the expression and localization of cell junctions [329]. Subsequently, the damaged cell junction proteins may be internalized and degraded within the host cell as shown before for VE-cadherin particularly [330,331].…”