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

J Cell Sci. 2015 Jan 15;128(2):364-72. doi: 10.1242/jcs.161323. Epub 2014 Nov 13.

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.

Keywords: AURKA; INPP5E; Primary cilium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism*
  • Cerebellum / abnormalities
  • Cerebellum / pathology
  • Cilia / genetics
  • Cilia / metabolism*
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Gene Expression Regulation
  • Humans
  • Kidney Diseases, Cystic / genetics
  • Kidney Diseases, Cystic / pathology
  • Mitosis / genetics
  • Mutation
  • Phosphatidylinositols / metabolism*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Protein Interaction Maps / genetics
  • Retina / abnormalities
  • Retina / pathology
  • Signal Transduction

Substances

  • Phosphatidylinositols
  • AURKA protein, human
  • Aurora Kinase A
  • Phosphoric Monoester Hydrolases
  • phosphoinositide 5-phosphatase

Supplementary concepts

  • Agenesis of Cerebellar Vermis