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

作　　者：Min Liu Wen Zhang Min Li Jiaxing Feng Wenjun Kuang Xiying Chen Feng Yang Qiang Sun Zhangqi Xu Jianfeng Hua Chunxia Yang Wei Liu Qiang Shu Yuehong Yang Tianhua Zhou Shanshan Xie 

机构地区：[1]The Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou,Zhejiang,China [2]Department of Cell Biology,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China [3]Institute of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China [4]Cancer Center,Zhejiang University,Hangzhou,Zhejiang,China [5]Department of Molecular Genetics,University of Toronto,Toronto,ON,Canada

出　　处：《Cell Research》2021年第11期1199-1211,共13页细胞研究（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31671394,31701214,91740205,and 31620103911);the National Key R&D Program of China(2019YFA0802202);the 111 Project(B13026).

摘　　要：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(UR)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 UR 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 UR 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.

关 键 词：MOTHER media SELECTIVE 

分 类 号：Q25[生物学—细胞生物学]