TCDB is operated by the Saier Lab Bioinformatics Group

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 4 TMS proteins (tetraspan proteins) that are constituents of tight junctions in animals. Although their specific functions are not yet clear, they are unique markers of any tight junction. They are present 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 it 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. Blasig et al. (2011) discussed a 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. 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).

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) (VS Reddy and MH Saier, Int J Bioinformatics, in press). Their inclusion in TCDB is therefore considered warranted.

References associated with 9.B.41 family:

Blasig, I.E., C. Bellmann, J. Cording, G. Del Vecchio, D. Zwanziger, O. Huber, and R.F. Haseloff. (2011). Occludin protein family: oxidative stress and reducing conditions. Antioxid Redox Signal 15: 1195-1219. 21235353
Franke, W.W. (2009). Discovering the molecular components of intercellular junctions--a historical view. Cold Spring Harb Perspect Biol 1: a003061. 20066111
Jin, Y., I. Uchida, K. Eto, T. Kitano, and S. Abe. (2008). Size-selective junctional barrier and Ca2+-independent cell adhesion in the testis of Cynops pyrrhogaster: expression and function of occludin. Mol Reprod Dev 75: 202-216. 17342736
Tash, B.R., M.C. Bewley, M. Russo, J.M. Keil, K.A. Griffin, J.M. Sundstrom, D.A. Antonetti, F. Tian, and J.M. Flanagan. (2012). The occludin and ZO-1 complex, defined by small angle X-ray scattering and NMR, has implications for modulating tight junction permeability. Proc. Natl. Acad. Sci. USA 109: 10855-10860. 22711802
Yaffe, Y., J. Shepshelovitch, I. Nevo-Yassaf, A. Yeheskel, H. Shmerling, J.M. Kwiatek, K. Gaus, M. Pasmanik-Chor, and K. Hirschberg. (2012). The MARVEL transmembrane motif of occludin mediates oligomerization and targeting to the basolateral surface in epithelia. J Cell Sci 125: 3545-3556. 22492786