Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants

Transporting epithelia provide a protective barrier against pathogenic insults while allowing the controlled exchange of ions, solutes and water with the external environment. In invertebrates, these functions depend on formation and maintenance of 'tight' septate junctions (SJs). However, the mechanism by which SJs affect transport competence and tissue homeostasis, and how these are modulated by ageing, remain incompletely understood. Here, we demonstrate that the Drosophila renal (Malpighian) tubules undergo an agedependent decline in secretory capacity, which correlates with mislocalisation of SJ proteins and progressive degeneration in cellular morphology and tissue homeostasis. Acute loss of the SJ protein Snakeskin in adult tubules induced progressive changes in cellular and tissue architecture, including altered expression and localisation of junctional proteins with concomitant loss of cell polarity and barrier integrity, demonstrating that compromised junctional integrity is sufficient to replicate these ageing-related phenotypes. Taken together, our work demonstrates a crucial link between homeostasis and organismal viability, as well as providing novel insights into the mechanisms underpinning ageing and renal disease.

Automated summary

This study found that the secretion capacity of Drosophila renal tubules declines with age, accompanied by mislocalisation of septate junction (SJ) proteins and progressive degeneration in cellular morphology. Acute loss of the SJ protein Snakeskin in adult tubules leads to changes in cellular and tissue structure, loss of cell polarity and barrier integrity. These findings demonstrate an important link between homeostasis and organismal viability, and provide new insights into the mechanisms underlying ageing and renal disease.