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

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

SUBMITTER: Plotnikova OV

PROVIDER: S-EPMC4294778 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Plotnikova Olga V OV Seo Seongjin S Cottle Denny L DL Conduit Sarah S Hakim Sandra S Dyson Jennifer M JM Mitchell Christina A CA Smyth Ian M IM

Journal of cell science 20141113 2

Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause the ciliopathies known as Joubert and MORM syndromes; however, the role of INPP5E in ciliary biology is not well understood. Here, we describe an interaction between INPP5E and AURKA, a centrosomal kinase that regulates mitosis and ciliary disassembly, and we show that this interaction is important for the stability of primary cilia. Furthermore, AURKA phosphorylates INPP5E and thereby increases its 5-phosphatase activity, which ...[more]

PMID: 25395580

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