Abstract
Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.
Highlights
Primary cilia are major cellular sensory organelles mediating the interaction between cells and external stimuli including chemical, mechanical, and paracrine signals
Sertraline induces the formation of primary cilia by suppressing cilia disassembly in human telomerase-immortalized retinal pigmented epithelial (htRPE) cells
To identify the chemical modulator of ciliogenesis, we developed a cell-based screening system using htRPE cells that stably expressing a fluorescent protein fused with Smo [17,18]
Summary
Primary cilia are major cellular sensory organelles mediating the interaction between cells and external stimuli including chemical, mechanical, and paracrine signals. Structural and functional abnormalities of cilia are associated with various human diseases known as ciliopathies, such as Bardet-Biedl syndrome, neurosensory impairment, renal polycystic diseases, diabetes, hypertension, and cancer [1,2,3]. The understanding of the regulation mechanism of ciliogenesis may useful in developing new therapeutic strategies against ciliopathies. Cilia are maintained by intraflagellar transport (IFT) mechanism, which moves non-membrane-bound particles and building materials from the cell body to the growing cilium [4]. PLOS ONE | DOI:10.1371/journal.pone.0118190 February 11, 2015
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