Dornan, A. J. , Halberg, K. V., Beuter, L.-K., Davies, S. A. and Dow, J. A.T. (2023) Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants. Journal of Cell Science, 136(19), jcs261118. (doi: 10.1242/jcs.261118) (PMID:37694602) (PMCID:PMC10565245)
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Abstract
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 septate junction protein Snakeskin in adult tubules induces 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 age-onset and renal disease.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by funding from UKRI BBSRC (BB/P008097/1 and BB/W002442/1) to SAD and JATD with additional funding given by the Villum Foundation (15365) and Danish Council for Independent Research Natural Sciences (9064-00009B) to KVH. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dow, Professor Julian and Davies, Professor Shireen and Halberg, Dr Kenneth and Dornan, Dr Anthony |
| Authors: | Dornan, A. J., Halberg, K. V., Beuter, L.-K., Davies, S. A., and Dow, J. A.T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Journal of Cell Science |
| Publisher: | Company of Biologists |
| ISSN: | 0021-9533 |
| ISSN (Online): | 1477-9137 |
| Published Online: | 11 September 2023 |
| Copyright Holders: | Copyright © 2023 Company of Biologists |
| First Published: | First published in Journal of Cell Science 136 (19): jcs261118 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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