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

Yasuhiro Yamamoto; Haruka Chino; Satoshi Tsukamoto; Koji L Ode; Hiroki R Ueda; Noboru Mizushima

doi:10.1038/s41467-021-23599-7

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

Nat Commun. 2021 Jun 2;12(1):3292. doi: 10.1038/s41467-021-23599-7.

Authors

Yasuhiro Yamamoto^{1

2}, Haruka Chino¹, Satoshi Tsukamoto³, Koji L Ode⁴, Hiroki R Ueda^{4

5}, Noboru Mizushima⁶

Affiliations

¹ Department of Biochemistry and Molecular Biology, The University of Tokyo, Tokyo, Japan.
² Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Laboratory Animal and Genome Sciences Section, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
⁴ Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Osaka, Japan.
⁶ Department of Biochemistry and Molecular Biology, The University of Tokyo, Tokyo, Japan. nmizu@m.u-tokyo.ac.jp.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Autophagy / genetics*
Brain / cytology
Brain / metabolism
Cell Line
Cilia / genetics
Cilia / metabolism*
Female
Fibroblasts / cytology
Fibroblasts / metabolism
Gene Expression Regulation
Kidney / cytology
Kidney / metabolism
Liver / cytology
Liver / metabolism
Male
Mice
Mice, Knockout
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Muscle, Skeletal / cytology
Muscle, Skeletal / metabolism
Myocardium / cytology
Myocardium / metabolism
Myosin Heavy Chains / genetics*
Myosin Heavy Chains / metabolism
NIMA-Related Kinases / deficiency
NIMA-Related Kinases / genetics*
Protein Binding
Sequence Alignment
Sequence Homology, Amino Acid
Sequestosome-1 Protein / genetics
Sequestosome-1 Protein / metabolism
Signal Transduction

Substances

Gabarapl1 protein, mouse
Microtubule-Associated Proteins
Myh9 protein, mouse
Sequestosome-1 Protein
Sqstm1 protein, mouse
NIMA-Related Kinases
Nek9 protein, mouse
Myosin Heavy Chains