INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability

Mutations in Inositol Polyphosphate-5-phosphatase E (INPP5E) cause the ciliopathies known as Joubert and MORM Syndromes; however the role of INPP5E in cilia biology is not well understood. We describe an interaction between INPP5E and AURKA, a centrosomal kinase that regulates mitosis and ciliary disassembly, and show this interaction is important for primary cilia stability. Furthermore, AURKA phosphorylates and thereby increases INPP5E 5-phosphatase activity, which in turn promotes transcriptional down-regulation of AURKA, partly via an AKT-dependent mechanism. These findings establish the first direct link between AURKA and phosphoinositide signalling and suggest the function of INPP5E in cilia is at least partly mediated by its interactions with AURKA