The primary cilium protein folliculin is part of the autophagy signaling pathway to regulate epithelial cell size in response to fluid flow.

Naïma Zemirli,Asma Boukhalfa,Nicolas Dupont,Etienne Morel,Patrice Codogno,Joëlle Botti

doi:10.15698/cst2019.03.180

Abstract

Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN is essential in the dialog between autophagy and the primary cilium in epithelial cells to integrate shear stress-dependent signaling.

Highlights

Autophagy is an evolutionary conserved stress-response process by which cells break down intracellular components, damaged organelles and proteins aggregates or pathogens, to ensure cellular quality control and homeostasis
Folliculin and autophagy are increased in response to fluid flow in HK2 cells We have recently shown that autophagy is induced in response to shear stress in mouse kidney epithelial cell (KEC) and in Madin-Darby canine kidney (MDCK) cells [2]
Upon shear stress the amount of FLCN protein increased in time, (Figure 1E and 1F), as was the FLCN mRNA (Figure 1G), suggesting that shear stress induction of autophagy leads to a specific upregulation of FLCN expression at the transcriptional level

Summary

Introduction

Autophagy is an evolutionary conserved stress-response process by which cells break down intracellular components, damaged organelles and proteins aggregates or pathogens, to ensure cellular quality control and homeostasis. It is induced in response to various stress types such as nutrient deprivation, cytotoxic agents, and hypoxia. We have recently shown that in kidney epithelial cells (KECs) autophagy is induced in response to fluid flow-provoked shear stress and that this fluid flow-dependent autophagy regulates cell volume [2]. We have demonstrated that shear stressinduced autophagy is triggered by a signaling cascade emanating from the primary cilium located at the apical side of epithelial cells [2]. The primary cilium, which is composed of a basal body and an axoneme, is a microtubulebased organelle present at the surface of various cell types [3] and plays a critical role in maintaining tissue homeostasis by sensing extracellular mechanical and chemical stimuli [4]

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Conclusion