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Phosphorylation-dependent Akt-Inversin interaction at the basal body of primary cilia
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Title: | Phosphorylation-dependent Akt-Inversin interaction at the basal body of primary cilia |
Authors: | Suizu, Futoshi Browse this author →KAKEN DB | Hirata, Noriyuki Browse this author | Kimura, Kohki Browse this author | Edamura, Tatsuma Browse this author | Tanaka, Tsutomu Browse this author | Ishigaki, Satoko Browse this author | Donia, Thoria Browse this author | Noguchi, Hiroko Browse this author | Iwanaga, Toshihiko Browse this author →KAKEN DB | Noguchi, Masayuki Browse this author →KAKEN DB |
Keywords: | Akt | Inversin | primary cilia | signal transduction |
Issue Date: | 15-Jun-2016 |
Publisher: | EMBO Press |
Journal Title: | EMBO Journal |
Volume: | 35 |
Issue: | 12 |
Start Page: | 1346 |
End Page: | 1363 |
Publisher DOI: | 10.15252/embj.201593003 |
Abstract: | A primary cilium is a microtubule-based sensory organelle that plays an important role in human development and disease. However, regulation of Akt in cilia and its role in ciliary development has not been demonstrated. Using yeast two-hybrid screening, we demonstrate that Inversin (INVS) interacts with Akt. Mutation in the INVS gene causes nephronophthisis type II (NPHP2), an autosomal recessive chronic tubulointerstitial nephropathy. Co-immunoprecipitation assays show that Akt interacts with INVS via the C-terminus. In vitro kinase assays demonstrate that Akt phosphorylates INVS at amino acids 864-866 that are required not only for Akt interaction, but also for INVS dimerization. Co-localization of INVS and phosphorylated form of Akt at the basal body is augmented by PDGF-AA. Akt-null MEF cells as well as siRNA-mediated inhibition of Akt attenuated ciliary growth, which was reversed by Akt reintroduction. Mutant phosphodeador NPHP2-related truncated INVS, which lack Akt phosphorylation sites, suppress cell growth and exhibit distorted lumen formation and misalignment of spindle axis during cell division. Further studies will be required for elucidating functional interactions of Akt-INVS at the primary cilia for identifying the molecular mechanisms underlying NPHP2. |
Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/62706 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 野口 昌幸
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