Tricellulin Forms a Barrier to Macromolecules in Tricellular Tight Junctions without Affecting Ion Permeability

Abstract

Tricellulin is a tight junction protein localized in tricellular tight junctions (tTJs), the meeting points of three cells, but also in bicellular tight junctions (bTJs). To investigate its specific barrier functions in bTJs and tTJs, TRIC-a was expressed in low-level tricellulin-expressing cells, and MDCK II, either in all TJs or only in tTJs. When expressed in all TJs, tricellulin increased paracellular electrical resistance and decreased permeability to ions and larger solutes, which are associated with enhanced ultrastructural integrity of bTJs toward enhanced strand linearity. In tTJs in contrast, ultrastructure was unchanged and tricellulin minimized permeability to macromolecules but not to ions. This paradox is explained by properties of the tTJ central tube which is wide enough for passage of macromolecules, but too rare to contribute significantly to ion permeability. In conclusion, at low tricellulin expression the tTJ central tube forms a pathway for macromolecules. At higher expression, tricellulin forms a barrier in tTJs effective only for macromolecules and in bTJs for solutes of all sizes.

Epidermal tight junctions in health and disease

“…When both TER and tracer flux change following a challenge (e.g., drugs, cytokines) it strongly indicates an effect on TJ function, with high TER and low permeability indicating increased and low TER and high permeability flux suggesting reduced TJ integrity. However, it is possible to observe changes in either the TJ ion or macromolecular permeability as an isolated event, independent of each other, 35 because ions and (larger) molecules are likely to use different pathways through the TJ. 36 Therefore, even isolated changes in TER without a change in tracer flux or vice versa may reflect TJ changes.…”

Tight junction protein gene expression patterns and changes in transcript abundance during development of model fish gill epithelia

“…In contrast, members of the recently proposed angulin family of proteins, consisting of tricellulin (Tric), lipolysis-stimulated lipoprotein receptor, and immunoglobulin-like domain-containing receptors 1 and 2, appear to make up the tTJ of vertebrates (Higashi et al, 2013). tTJ proteins have also been reported to contribute to the barrier properties of vertebrate epithelia (Furuse et al, 2012;Ikenouchi et al, 2005;Korompay et al, 2012;Krug et al, 2009;Masuda et al, 2010;Ohkuni et al, 2009;Takasawa et al, 2013;.…”

TNFα-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFκB signaling

“…Among the transmembrane proteins located in TJ strands are occludin, tricellulin, junctional adhesion molecule and the claudin family, the latter has a pivotal role in intestinal barrier function (Amasheh et al, 2002;Furuse et al, 1993;Ikenouchi et al, 2005;Krug et al, 2009a;Bazzoni, 2003;Tsukita et al, 2001;Krause et al, 2008). Although several claudins have been identified to form barriers, a few members of this family also form paracellular channels, for example, claudin-2, claudin-10A and claudin-10B (Amasheh et al, 2002;Günzel et al, 2009).…”