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

Dornan, A.J. , Halberg, K.A., Beuter, L.-K., Davies, S.-A. and Dow, J.A.T. (2020) The septate junction protein Snakeskin is critical for epithelial barrier function and tissue homeostasis in the Malpighian tubules of adult Drosophila. bioRxiv, (doi: 10.1101/2020.12.14.422678)

Abstract

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 tubule’s 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.

• Item Type: Articles
• Additional Information: This work was supported by funding from UKRI BBSRC (BB/P008097/1) to SAD and JATD with additional funding given by the Villum Foundation (15365) to KAH.
• Keywords: Drosophila, Malpighian tubule, smooth septate junction, Snakeskin, polarity, epithelial barrier function, ageing.
• Status: Published
• Refereed: No
• 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.A., Beuter, L.-K., Davies, S.-A., and Dow, J.A.T.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: bioRxiv
• Copyright Holders: Copyright © The Author(s) 2020
• First Published: First published in bioRxiv 15 December 2020
• Publisher Policy: Reproduced under a creative commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173817		Functional analysis of insect neuropeptide G protein-coupled receptors	Shireen Davies	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/P008097/1	MCSB - Integrative & Systems Biology