The septate junction protein Snakeskin is critical for epithelial barrier function and tissue homeostasis in the Malpighian tubules of adult Drosophila

Transporting epithelia provide a protective physical barrier while directing appropriate transport of ions, solutes and water. In invertebrates, epithelial integrity is dependent on formation, and maintenance, of tight septate junctions (SJs). We demonstrated that Drosophila Malpighian (renal) tubules undergo an age-dependent decline in secretory transport capacity, which correlates with mislocalisation of SJ proteins and coincident progressive degeneration in cellular morphology and tissue homeostasis. By restrictively impairing, in adult tubules, the cell adhesion protein Snakeskin, which is essential for smooth SJ formation, we observed progressive changes in cellular and tissue morphology that phenocopied these effects, including mislocalisation of junctional proteins with concomitant loss of cell polarity and barrier function. Resulting in significant accelerated decline in tubule secretory capacity and organismal viability. Our investigations highlight the tubules essential role in maintenance of organismal health, while providing measurable markers of compromised epithelial barrier and tissue function that manifest in advanced morbidity and death. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/422678v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@68e080org.highwire.dtl.DTLVardef@16af9ddorg.highwire.dtl.DTLVardef@3a399eorg.highwire.dtl.DTLVardef@9cc393_HPS_FORMAT_FIGEXP M_FIG Model for epithelial dysfunction arising from failure of smooth septate junctional complexes as a consequence of impaired Snakeskin expression. C_FIG