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

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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 age-dependent 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 epithelial barrier integrity, tubule transport competence, renal homeostasis and organismal viability, as well as providing novel insights into the mechanisms underpinning ageing and renal disease.
OriginalsprogEngelsk
Artikelnummerjcs261118
TidsskriftJournal of Cell Science
Vol/bind136
Udgave nummer19
Antal sider15
ISSN0021-9533
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This work was supported by funding from the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council (BBSRC) (BB/P008097/1 and BB/W002442/1) to S.-A.D. and J.A.T.D., with additional funding given by the Villum Fonden (15365) and the Danish Council for Independent Research Natural Sciences (Danmarks Frie Forskningsfond; 9064-00009B) to K.V.H. Open Access funding provided by University of Glasgow. Deposited in PMC for immediate release.

Funding Information:
The notion that impairment of junctional complexes in a specific sub-population of cells affects overall tissue function and morphology implies that non-cell-autonomous communication(s) are required across these tight junctions. This is supported by the

Publisher Copyright:
© 2023. Published by The Company of Biologists Ltd.

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