Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites

The primary cilium is a microtubule-based organelle that functions in sensory and signal transduction; the authors demonstrate here that autophagic degradation of the oral-facial-digital syndrome 1 (OFD1) protein at centriolar satellites promotes primary cilium biogenesis, and that autophagy modulation might provide a novel means of ciliopathy treatment. Autophagy's links with 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. The primary cilium is a microtubule-based organelle that functions in sensory and signalling pathways. Defects in ciliogenesis can lead to a group of genetic syndromes known as ciliopathies 1 , 2 , 3 . However, the regulatory mechanisms of primary ciliogenesis in normal and cancer cells are incompletely understood. Here we demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral-facial-digital syndrome 1), at centriolar satellites promotes primary cilium biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles and protein aggregates are engulfed in autophagosomes and delivered to lysosomes for destruction 4 . We show that the population of OFD1 at the centriolar satellites is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient Atg5 or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar satellites, leading to fewer and shorter primary cilia and a defective recruitment of BBS4 (Bardet–Biedl syndrome 4) to cilia. These defects are fully rescued by OFD1 partial knockdown that reduces the population of OFD1 at centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites promotes cili