NudCL2 is an autophagy receptor that mediates selective autophagic degradation of CP110 at mother centrioles to promote ciliogenesis

Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the...

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Published in:Cell research 2021-11, Vol.31 (11), p.1199-1211
Main Authors: Liu, Min, Zhang, Wen, Li, Min, Feng, Jiaxing, Kuang, Wenjun, Chen, Xiying, Yang, Feng, Sun, Qiang, Xu, Zhangqi, Hua, Jianfeng, Yang, Chunxia, Liu, Wei, Shu, Qiang, Yang, Yuehong, Zhou, Tianhua, Xie, Shanshan
Format: Article
Language:English
Subjects:
Animals
Autophagy
Capping
Centrioles
Cilia
Coils
Defects
Degradation
Depletion
Embryos
Female
Homeostasis
Humans
Microtubule-Associated Proteins - genetics
Mothers
Mutants
Phagocytosis
Phenotypes
Proteins
Receptors
Vertebrates
Zebrafish
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Summary:Primary cilia extending from mother centrioles are essential for vertebrate development and homeostasis maintenance. Centriolar coiled-coil protein 110 (CP110) has been reported to suppress ciliogenesis initiation by capping the distal ends of mother centrioles. However, the mechanism underlying the specific degradation of mother centriole-capping CP110 to promote cilia initiation remains unknown. Here, we find that autophagy is crucial for CP110 degradation at mother centrioles after serum starvation in MEF cells. We further identify NudC-like protein 2 (NudCL2) as a novel selective autophagy receptor at mother centrioles, which contains an LC3-interacting region (LIR) motif mediating the association of CP110 and the autophagosome marker LC3. Knockout of NudCL2 induces defects in the removal of CP110 from mother centrioles and ciliogenesis, which are rescued by wild-type NudCL2 but not its LIR motif mutant. Knockdown of CP110 significantly attenuates ciliogenesis defects in NudCL2-deficient cells. In addition, NudCL2 morphants exhibit ciliation-related phenotypes in zebrafish, which are reversed by wild-type NudCL2, but not its LIR motif mutant. Importantly, CP110 depletion significantly reverses these ciliary phenotypes in NudCL2 morphants. Taken together, our data suggest that NudCL2 functions as an autophagy receptor mediating the selective degradation of mother centriole-capping CP110 to promote ciliogenesis, which is indispensable for embryo development in vertebrates.
ISSN:1001-0602
1748-7838
DOI:10.1038/s41422-021-00560-3