# Elevated Piezo levels cause structural and functional alterations in Drosophila garland nephrocytes

## TL;DR

High levels of Piezo in fruit fly nephrocytes lead to structural and functional changes, including increased stress fibers and mitochondrial activity.

## Contribution

The study reveals novel functional and morphological effects of elevated Piezo levels in Drosophila nephrocytes.

## Key findings

- Elevated Piezo levels cause accumulation of actin stress fibres and increased Cubilin expression.
- Increased Piezo levels are associated with more acidic vesicles and elevated mitochondrial mass/activity.
- High Piezo levels lead to elevated superoxide levels and functional disturbances in nephrocytes.

## Abstract

Elevated Piezo levels cause morphological and functional alterations in garland nephrocytes, as well as accumulation of actin stress fibres, increased Cubilin expression, more acidic vesicles, increased mitochondrial mass and/or activity, and elevated superoxide levels.

Podocytes, epithelial cells of the glomerular filtration barrier, are constantly exposed to biomechanical forces. These include hydrostatic pressure and shear stress, which increase during diseases such as hypertension or diabetes. To sense and respond to such changes in their physical environment, podocytes express mechanosensors and mechanotransducers. To deepen our knowledge about renal mechanotransduction mechanisms, we used Drosophila nephrocytes. Nephrocytes and mammalian podocytes are highly similar in morphology and molecular make-up of the filtration barrier; thus, nephrocytes are considered the homologue cells to podocytes. In addition, nephrocytes also experience biomechanical forces because of haemolymph movement. Here, we investigated the role of the mechanotransducer Piezo in larval garland nephrocytes. Depletion of Piezo produces only a mild functional phenotype, whereas elevated Piezo levels result in a severe phenotype with functional and morphological disturbances. Increased Piezo levels also cause the accumulation of actin stress fibres, increased Cubilin expression, more acidic vesicles, increased mitochondrial mass and/or activity, and elevated superoxide levels.