Abstract
BackgroundTight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction.ResultsHere we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link) domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance.ConclusionsOur data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.
Highlights
Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge
Expression of MarvelD3 in epithelial and endothelial cells Bioinformatics analysis revealed the existence of two human MarvelD3 isoforms: isoform 1 contains 410 amino acids [Genbank: NM_001017967] and isoform 2 401 amino acids [Genbank: NM_052858] (Fig. 1A)
Database searches revealed that MarvelD3 is expressed in chicken, Xenopus and various mammalian species, but not in any invertebrates, suggesting that it is expressed by vertebrates only (Fig. 1B and Table 1)
Summary
Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Tight junctions participate in the establishment and maintenance of cell polarity and in various signalling pathways controlling gene expression, cell differentiation and proliferation. Their ability to perform (page number not for citation purposes). The single-span proteins (e.g., JAMs, Crb3) as well as Bves, a protein with three transmembrane domains, serve different types of regulatory and signalling functions during differentiation, junction assembly, and transmigration of leukocytes [5,6,7,8,9]
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