The Role Of Several Prominent Claudin Tight Junction Proteins In Teleost Fish Gill Epithelium Paracellular Permeability

Because the internal fluids of freshwater (FW) teleost fishes are hyperosmotic relative to their surroundings, these organisms experience obligatory ion loss across epithelia that directly interface with water (e.g. the gill epithelium). In FW fishes, the tight junction (TJ) complex is broadly acknowledged to limit paracellular ion loss across the gill epithelium as it occludes the paracellular cleft and therefore acts as a barrier to impede paracellular solute movement. The vertebrate TJ complex is composed of numerous TJ proteins and the major proportion of these belong to the claudin (Cldn) superfamily. Cldn TJ proteins are not only implicated in regulating general permeability but also ion‐specific permselectivity of various vertebrate epithelia. Several Cldns seem to be particularly important for the establishment and maintenance of the barrier properties of the fish gill epithelium. Additionally several important ionoregulatory hormones in teleost fishes (e.g. cortisol), have been implicated in the regulation of paracellular permeability of FW teleost fish gill epithelia by exerting their actions on specific Cldns and other TJ proteins. Nevertheless, a clear picture of how paracellular movement of specific ions is regulated by the complex molecular architecture of TJs in an architecturally complex epithelium is only beginning to emerge. This has been achieved in part, by using primary cultured ‘reconstructed’ gill epithelia composed of different gill cell types. These architecturally simple models permit endpoints of transepithelial and paracellular permeability to be measured across a tissue that otherwise exhibits a restrictive morphology and problematic cellular heterogeneity. This can be done in the presence of ionoregulatory hormones and measurements of permeability can then be coupled with manipulations of TJ architecture via transcriptional knockdown of TJ proteins using dsRNA. This study will present an examination of the contribution of several Cldns to gill epithelium permeability as well as endocrine mechanisms regulating TJ protein abundance in the gill epithelium. Particular attention has been paid to the compensatory response caused by transcriptional knockdown of specific Cldns in the gill epithelium of fish as this area has been entirely overlooked, despite the fact that the teleost genome is well known to possess a particularly large number of Cldn genes due to teleost‐specific genome duplication events. Support or Funding Information This work was funded by National Science and Engineering Research Council of Canada