# Polycystin-2 Mediated Calcium Signalling in the Dictyostelium Model for Autosomal Dominant Polycystic Kidney Disease

## TL;DR

This study uses Dictyostelium to investigate how Polycystin-2 regulates calcium signaling, which is disrupted in a kidney disease called ADPKD.

## Contribution

The study demonstrates that Dictyostelium is a useful model for understanding Polycystin-2's role in calcium signaling.

## Key findings

- Overexpression of Polycystin-2 increases chemoattractant-stimulated calcium response magnitudes.
- Polycystin-2 knockdown reduces basal cytosolic calcium levels and alters downstream calcium-sensitive processes.
- Calcium signaling changes affect growth, endocytosis, and cell differentiation in Dictyostelium.

## Abstract

Autosomal dominant polycystic kidney disease (ADPKD) occurs when the proteins Polycystin-1 (PC1, PKD1) and Polycystin-2 (PC2, PKD2) contain mutations. PC1 is a large membrane receptor that can interact and form a complex with the calcium-permeable cation channel PC2. This complex localizes to the plasma membrane, primary cilia and ER. Dysregulated calcium signalling and consequential alterations in downstream signalling pathways in ADPKD are linked to cyst formation and expansion; however, it is not completely understood how PC1 and PC2 regulate calcium signalling. We have studied Polycystin-2 mediated calcium signalling in the model organism Dictyostelium discoideum by overexpressing and knocking down the expression of the endogenous Polycystin-2 homologue, Polycystin-2. Chemoattractant-stimulated cytosolic calcium response magnitudes increased and decreased in overexpression and knockdown strains, respectively, and analysis of the response kinetics indicates that Polycystin-2 is a significant contributor to the control of Ca2+ responses. Furthermore, basal cytosolic calcium levels were reduced in Polycystin-2 knockdown transformants. These alterations in Ca2+ signalling also impacted other downstream Ca2+-sensitive processes including growth rates, endocytosis, stalk cell differentiation and spore viability, indicating that Dictyostelium is a useful model to study Polycystin-2 mediated calcium signalling.