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Age-related decline of occluding junctions in Drosophila melanogaster


Intestinal barrier function declines across species with age, including Drosophila melanogaster, and the causes are unknown. Occluding junctions, referred to as tight junctions (TJs) in mammals and septate junctions (SJs) in arthropods, contribute significantly to the maintenance of intestinal barrier function. The tricellular septate junction (tSJ) is at the point where three adjacent cells meet. Our lab previously demonstrated that aging results in mis-localization of the tricellular SJ (tSJ)-specific component Gliotactin (Gli) in enterocytes (ECs) of the fly intestine. Because we found Gli is required at the tSJ to maintain intestinal homeostasis, we decided to investigate the tSJ protein Bark beetle (Bark) to find if it is similarly required. Like Gli, Bark appears to mislocalize away from the tSJ in aged fly intestines. EC-specific bark depletion in young flies disrupted intestinal stem cell homeostasis, compromised intestinal barrier function, and shortened lifespan. We concluded that Bark is required at the tSJ to maintain intestinal homeostasis, and that mislocalization of Bark in aged flies may contribute to the overall intestinal aging phenotype. Additionally, we had previous evidence that suggested age-related SJ protein mislocalization is due to changes in vesicular trafficking. Our preliminary data indicates early and late endosomes may increase in size or aggregation in the aged fly intestine, and SJ proteins Mesh and Gli may respectively accumulate in each compartment. The endocytosis pathway also appears to be required for normal SJ protein localization in the intestine. Future studies will further characterize age-related changes in vesicular trafficking in the fly intestine, which may be beneficial for prevention of age-related intestinal barrier decline in humans.

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