Volume 31, No 11, Nov 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 11, November 2021: 1199-1211   |  Open Access

ORIGINAL ARTICLES

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

Min Liu¹ , Wen Zhang^2,3,† , Min Li² , Jiaxing Feng² , Wenjun Kuang² , Xiying Chen² , Feng Yang² , Qiang Sun² , Zhangqi Xu² , Jianfeng Hua² , Chunxia Yang² , Wei Liu² , Qiang Shu¹ , Yuehong Yang² , Tianhua Zhou^2,3,4,5,* , Shanshan Xie^1,*

¹The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China
²Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
³Institute of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
⁴Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
⁵Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
^†These authors contributed equally: Min Liu, Wen Zhang
Correspondence: Tianhua Zhou(tzhou@zju.edu.cn)Shanshan Xie(sxie@zju.edu.cn)

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.

https://doi.org/10.1038/s41422-021-00560-3

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