LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110–CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlyi...

Full description

Saved in:
Bibliographic Details
Published inThe Journal of cell biology Vol. 221; no. 1
Main Authors Shen, Xiao-Lin, Yuan, Jin-Feng, Qin, Xuan-He, Song, Guang-Ping, Hu, Huai-Bin, Tu, Hai-Qing, Song, Zeng-Qing, Li, Pei-Yao, Xu, Yu-Ling, Li, Sen, Jian, Xiao-Xiao, Li, Jia-Ning, He, Chun-Yu, Yu, Xi-Ping, Liang, Li-Yun, Wu, Min, Han, Qiu-Ying, Wang, Kai, Li, Ai-Ling, Zhou, Tao, Zhang, Yu-Cheng, Wang, Na, Li, Hui-Yan
Format Journal Article
LanguageEnglish
Published United States Rockefeller University Press 03.01.2022
Subjects
Animals
Cell Cycle Proteins - metabolism
Cell Line
Centrioles - metabolism
Chains
Cilia
Cilia - metabolism
Development
Embryogenesis
Embryonic growth stage
Humans
Mice
Microtubule-Associated Proteins - metabolism
mRNA
Multiprotein Complexes
Organogenesis
Phosphoproteins - metabolism
RNA-Binding Proteins - metabolism
Splicing
Splicing factors
Substrate Specificity
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitination
Zebrafish
Online AccessGet full text

Cover

More Information
Summary:Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110–CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110–CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
X.-L. Shen and J.-F. Yuan contributed equally to this paper.
ISSN:0021-9525
1540-8140
1540-8140
DOI:10.1083/jcb.202105092