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Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants
Anthony J Dornan1, Kenneth V Halberg2, Liesa-Kristin Beuter1,3
1School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Journal of Cell Science
|September 11, 2023
Summary
Aging impairs epithelial barrier function and transport, leading to renal decline. Loss of septate junctions (SJs) in Drosophila tubules causes age-like degeneration, highlighting SJ integrity
Area of Science:
- Epithelial biology
- Renal physiology
- Aging research
Background:
- Transporting epithelia form essential barriers and regulate transport via septate junctions (SJs).
- The role of SJs in transport competence, homeostasis, and aging remains unclear.
Purpose of the Study:
- To investigate the impact of aging on epithelial transport and SJ integrity in Drosophila renal tubules.
- To elucidate the mechanisms linking SJ dysfunction to age-related renal decline.
Main Methods:
- Age-dependent analysis of Drosophila renal (Malpighian) tubules.
- Assessment of secretory capacity, cellular morphology, and SJ protein localization.
- Experimental disruption of the SJ protein Snakeskin in adult tubules.
Main Results:
- Ageing correlates with reduced secretory capacity, SJ protein mislocalization, and tissue degeneration in Drosophila tubules.
- Acute loss of Snakeskin recapitulates age-related phenotypes, including loss of cell polarity and barrier integrity.
- Compromised SJ integrity is sufficient to induce age-like changes in renal tubule architecture and function.
Conclusions:
- Epithelial barrier integrity, regulated by SJs, is critical for renal transport competence and homeostasis.
- Age-dependent decline in SJ function contributes to renal aging and disease.
- This study provides insights into the mechanisms of aging and renal dysfunction.
