Functional interaction between autophagy and ciliogenesis

Nutrient deprivation is a stimulus shared by both autophagy and the formation of primary cilia. The recently discovered role of primary cilia in nutrient sensing and signalling motivated us to explore the possible functional interactions between this signalling hub and autophagy. Here we show that part of the molecular machinery involved in ciliogenesis also participates in the early steps of the autophagic process. Signalling from the cilia, such as that from the Hedgehog pathway, induces autophagy by acting directly on essential autophagy-related proteins strategically located in the base of the cilium by ciliary trafficking proteins. Whereas abrogation of ciliogenesis partially inhibits autophagy, blockage of autophagy enhances primary cilia growth and cilia-associated signalling during normal nutritional conditions. We propose that basal autophagy regulates ciliary growth through the degradation of proteins required for intraflagellar transport. Compromised ability to activate the autophagic response may underlie some common ciliopathies. The primary cilium is a microtubule-based organelle that functions in sensory and signal transduction; here the authors show that the primary cilium is required for activation of starvation-induced autophagy and that basal autophagy negatively regulates ciliogenesis. The primary cilium is a non-motile signalling organelle found in a specific region of the plasma membrane where it functions in both signal transduction and sensing environmental cues such as nutrient levels. Two complementary papers published in this week's issue of Nature describe a novel link between ciliogenesis and autophagy. Zaiming Tang et al. demonstrate that autophagic degradation of a negative regulator of cilia formation, oral-facial-digital syndrome 1 (OFD1), at centriolar satellites promotes primary cilium biogenesis. Olatz Pampliega et al. uncover a reciprocal relationship between ciliogenesis and autophagy and show that the primary cilium is required for activation of starvation-induced autophagy, and that autophagy negatively regulates ciliogenesis. Cross-talk between the primary cilium and the autophagy pathway may further lead to our understanding of human ciliary diseases.