Store-operated calcium entry inhibits primary ciliogenesis via the activation of Aurora A

Abstract

The primary cilium is an antenna-like organelle protruding from the cell surface that can detect physical and chemical stimuli in the extracellular space to activate specific signaling pathways and downstream gene expressions. Calcium ion (Ca²⁺ ) signaling regulates a wide spectrum of cellular processes, including fertilization, proliferation, differentiation, muscle contraction, migration, and death. This study investigated the effects of the regulation of cytosolic Ca²⁺ levels on ciliogenesis using chemical, genetic, and optogenetic approaches. We found that ionomycin-induced Ca²⁺ influx inhibited ciliogenesis and Ca²⁺ chelator BATPA-AM-induced Ca²⁺ depletion promoted ciliogenesis. In addition, store-operated Ca²⁺ entry and the endoplasmic reticulum Ca²⁺ sensor stromal interaction molecule 1 (STIM1) negatively regulated ciliogenesis. Moreover, an optogenetic platform was used to create different Ca²⁺ oscillation patterns by manipulating lighting parameters, including density, frequency, exposure time, and duration. Light-activated Ca²⁺ -translocating channelrhodopsin (CatCh) is activated by 470-nm blue light to induce Ca²⁺ influx. Our results show that high-frequency Ca²⁺ oscillations decrease ciliogenesis. Furthermore, the inhibition of cilia formation induced by Ca²⁺ may occur via the activation of Aurora kinase A. Cilia not only induce Ca²⁺ signaling but also regulate cilia formation by Ca²⁺ signaling.

Keywords: Aurora A; calcium; optogenetics; primary cilia; store-operated Ca2+ entry.