Abstract
Angulin-2/ILDR1 is a member of the angulin protein family, which is exclusively expressed at tricellular tight junctions in epithelia. Tricellular tight junctions are found where three cells meet and where three bicellular tight junction strands converge. Tricellular tight junctions are thought to be important for paracellular permeability of ions and water in epithelial tissues. It was recently reported that angulin-2/ILDR1 knockout mice have water transport abnormalities in the kidney. Since angulin-2/ILDR1 is the main tricellular tight junction protein in the large intestine, the goal of this research was to examine the effect of angulin-2/ILDR1 knockout on large intestinal paracellular water transport. We found that Ildr1 knockout mice showed no detectable phenotype other than deafness. In addition, paracellular transport as assessed by Ussing chamber was unchanged in Ildr1 knockout mice. However, we found that in the colon and the kidney of Ildr1 knockout mice, another tricellular tight junction protein, angulin-1/LSR, changes its expression pattern. We propose that with this replacement in tissue localization, angulin-1/LSR compensates for the loss of angulin-2/ILDR1 and maintains the barrier and function of the epithelia in the large intestine as well as the kidney.
Highlights
Angulin-2/ILDR1 is a member of the angulin protein family, which is exclusively expressed at tricellular tight junctions in epithelia
BTJ are not thought to be the main route of paracellular water transport and it is theorized that tricellular tight junctions (TJ) instead are important for water a bsorption[18]
To investigate the reason for this, we examined the mRNA levels of the tricellular TJ (tTJ) proteins, which are tricellulin, angulin-1 (LSR), angulin-2 (ILDR1), and angulin-3 (ILDR2)[33]
Summary
Angulin-2/ILDR1 is a member of the angulin protein family, which is exclusively expressed at tricellular tight junctions in epithelia. The mechanism of water transport is explained by the standing gradient theory, which assumes the lateral intracellular spaces between cells to be cylindrical tubes, with a closed and open end, where active transport of solute occurs near the closed end (tight junctions) and osmotic transport of water follows, which creates an osmotic gradient along the length of the channel[14]. This theory explains how water can be absorbed isotonically from the small intestinal lumen to blood. BTJ are not thought to be the main route of paracellular water transport and it is theorized that tricellular TJ (tTJ) instead are important for water a bsorption[18]
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