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

Olga V Plotnikova; Seongjin Seo; Denny L Cottle; Sarah Conduit; Sandra Hakim; Jennifer M Dyson; Christina A Mitchell; Ian M Smyth

doi:10.1242/jcs.161323

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

Journal article

Open access

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

Olga V Plotnikova, Seongjin Seo, Denny L Cottle, Sarah Conduit, Sandra Hakim, Jennifer M Dyson, Christina A Mitchell and Ian M Smyth

Journal of cell science, Vol.128(2), pp.364-372

01/15/2015

DOI: 10.1242/jcs.161323

PMCID: PMC4294778

PMID: 25395580

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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.

Abnormalities, Multiple - pathology

Phosphoric Monoester Hydrolases - genetics

Signal Transduction

Humans

Gene Expression Regulation

Cerebellum - abnormalities

Eye Abnormalities - genetics

Mitosis - genetics

Aurora Kinase A - metabolism

Cilia - metabolism

Cerebellum - pathology

Cilia - genetics

Kidney Diseases, Cystic - pathology

Eye Abnormalities - pathology

Protein Interaction Maps - genetics

Retina - abnormalities

Kidney Diseases, Cystic - genetics

Phosphatidylinositols - metabolism

Mutation

Phosphoric Monoester Hydrolases - metabolism

Retina - pathology

Abnormalities, Multiple - genetics

Aurora Kinase A - genetics

Details

Title: Subtitle: INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability
Creators: Olga V Plotnikova - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Seongjin Seo - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242
Denny L Cottle - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Sarah Conduit - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Sandra Hakim - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Jennifer M Dyson - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Christina A Mitchell - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia
Ian M Smyth - Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia ian.smyth@monash.edu
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.128(2), pp.364-372
DOI: 10.1242/jcs.161323
PMID: 25395580
PMCID: PMC4294778
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: England
Grant note: R01 EY022616 / NEI NIH HHS
Language: English
Date published: 01/15/2015
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980063402771

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