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NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA

Author

Listed:
  • Yasuhiro Yamamoto

    (The University of Tokyo
    The University of Tokyo)

  • Haruka Chino

    (The University of Tokyo)

  • Satoshi Tsukamoto

    (National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology)

  • Koji L. Ode

    (The University of Tokyo)

  • Hiroki R. Ueda

    (The University of Tokyo
    Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research)

  • Noboru Mizushima

    (The University of Tokyo)

Abstract

Autophagy regulates primary cilia formation, but the underlying mechanism is not fully understood. In this study, we identify NIMA-related kinase 9 (NEK9) as a GABARAPs-interacting protein and find that NEK9 and its LC3-interacting region (LIR) are required for primary cilia formation. Mutation in the LIR of NEK9 in mice also impairs in vivo cilia formation in the kidneys. Mechanistically, NEK9 interacts with MYH9 (also known as myosin IIA), which has been implicated in inhibiting ciliogenesis through stabilization of the actin network. MYH9 accumulates in NEK9 LIR mutant cells and mice, and depletion of MYH9 restores ciliogenesis in NEK9 LIR mutant cells. These results suggest that NEK9 regulates ciliogenesis by acting as an autophagy adaptor for MYH9. Given that the LIR in NEK9 is conserved only in land vertebrates, the acquisition of the autophagic regulation of the NEK9–MYH9 axis in ciliogenesis may have possible adaptive implications for terrestrial life.

Suggested Citation

  • Yasuhiro Yamamoto & Haruka Chino & Satoshi Tsukamoto & Koji L. Ode & Hiroki R. Ueda & Noboru Mizushima, 2021. "NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23599-7
    DOI: 10.1038/s41467-021-23599-7
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    Cited by:

    1. Muqing Cao & Xiaoxiao Zou & Chaoyi Li & Zaisheng Lin & Ni Wang & Zhongju Zou & Youqiong Ye & Joachim Seemann & Beth Levine & Zaiming Tang & Qing Zhong, 2023. "An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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