A look at tricellulin and its role in tight junction formation and maintenance

Tight junctions are elaborate networks of transmembrane and cytosolic proteins that regulate epithelial permeability. Tricellulin was the first tight junction protein found at tricellular tight junctions, the specialized structures occurring where three cells meet together. Here, we summarize the current knowledge about tricellulin (marvelD2), a MARVEL domain protein. We address tricellulin location at tricellular junctions, and establish the comparison with the other members of the MARVEL family, occludin (marvelD1) and marvelD3. The structure of tricellulin and its membrane folding, as well as the proposed molecular interactions of tricellulin with other tight junction proteins, together with the interplay between those proteins are also discussed. In addition, we address the role of tricellulin in barrier properties, discriminating the involvement of the protein in paracellular permeability at bicellular and at tricellular tight junctions. Moreover, the key importance of the protein for hearing is highlighted based on the fact that mutations in TRIC, the human tricellulin gene, lead to deafness. Furthermore, this review points to some of the aspects that still deserve clarification for a better understanding of the biology of tight junctions in general and of tricellulin in particular.