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

Olga Plotnikova, Seongjin Seo, Denny L Cottle, Sarah E Conduit, Sandra Hakim, Jennifer M Dyson, Christina Anne Mitchell, Ian M Smyth

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalJournal of Cell Science
Volume128
Issue number2
DOIs
Publication statusPublished - 2015

Cite this

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title = "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 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.",
author = "Olga Plotnikova and Seongjin Seo and Cottle, {Denny L} and Conduit, {Sarah E} and Sandra Hakim and Dyson, {Jennifer M} and Mitchell, {Christina Anne} and Smyth, {Ian M}",
year = "2015",
doi = "10.1242/jcs.161323",
language = "English",
volume = "128",
pages = "364--372",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists",
number = "2",

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INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability. / Plotnikova, Olga; Seo, Seongjin; Cottle, Denny L; Conduit, Sarah E; Hakim, Sandra; Dyson, Jennifer M; Mitchell, Christina Anne; Smyth, Ian M.

In: Journal of Cell Science, Vol. 128, No. 2, 2015, p. 364-372.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - INPP5E interacts with AURKA, linking phosphoinositide signaling to primary cilium stability

AU - Plotnikova, Olga

AU - Seo, Seongjin

AU - Cottle, Denny L

AU - Conduit, Sarah E

AU - Hakim, Sandra

AU - Dyson, Jennifer M

AU - Mitchell, Christina Anne

AU - Smyth, Ian M

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294778/

U2 - 10.1242/jcs.161323

DO - 10.1242/jcs.161323

M3 - Article

VL - 128

SP - 364

EP - 372

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 2

ER -