Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants
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Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants. / Dornan, Anthony J.; Halberg, Kenneth V.; Beuter, Liesa Kristin; Davies, Shireen Anne; Dow, Julian A.T.
In: Journal of Cell Science, Vol. 136, No. 19, jcs261118, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants
AU - Dornan, Anthony J.
AU - Halberg, Kenneth V.
AU - Beuter, Liesa Kristin
AU - Davies, Shireen Anne
AU - Dow, Julian A.T.
N1 - Publisher Copyright: © 2023. Published by The Company of Biologists Ltd.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Ageing
KW - Drosophila
KW - Epithelial barrier function
KW - Malpighian tubule
KW - Polarity
KW - Smooth septate junction
KW - Snakeskin
U2 - 10.1242/jcs.261118
DO - 10.1242/jcs.261118
M3 - Journal article
C2 - 37694602
AN - SCOPUS:85176258429
VL - 136
JO - Journal of Cell Science
JF - Journal of Cell Science
SN - 0021-9533
IS - 19
M1 - jcs261118
ER -
ID: 373660057