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Phosphorylation‐dependent Akt–Inversin interaction at the basal body of primary cilia
Author(s) -
Suizu Futoshi,
Hirata Noriyuki,
Kimura Kohki,
Edamura Tatsuma,
Tanaka Tsutomu,
Ishigaki Satoko,
Donia Thoria,
Noguchi Hiroko,
Iwanaga Toshihiko,
Noguchi Masayuki
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593003
Subject(s) - biology , phosphorylation , cilium , basal body , basal (medicine) , microbiology and biotechnology , protein kinase b , primary (astronomy) , proto oncogene proteins c akt , biochemistry , endocrinology , flagellum , physics , astronomy , insulin , gene
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 ( NPHP 2), 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 si RNA ‐mediated inhibition of Akt attenuated ciliary growth, which was reversed by Akt reintroduction. Mutant phosphodead‐ or NPHP 2‐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 NPHP 2.