气候变化领域集成服务门户(CCPortal): A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability

CCPortal

DOI	10.1073/pnas.2018740118
	A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability
	Loukil A.; Barrington C.; Goetz S.C.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	Cilia biogenesis is a complex, multistep process involving the coordination of multiple cellular trafficking pathways. Despite the importance of ciliogenesis in mediating the cellular response to cues from the microenvironment, we have only a limited understanding of the regulation of cilium assembly. We previously identified Tau tubulin kinase 2 (TTBK2) as a key regulator of ciliogenesis. Here, using CRISPR kinome and biotin identification screening, we identify the CK2 catalytic subunit CSNK2A1 as an important modulator of TTBK2 function in cilia trafficking. Superresolution microscopy reveals that CSNK2A1 is a centrosomal protein concentrated at the mother centriole and associated with the distal appendages. Csnk2a1 mutant cilia are longer than those of control cells, showing instability at the tip associated with ciliary actin cytoskeleton changes. These cilia also abnormally accumulate key cilia assembly and SHH-related proteins. De novo mutations of Csnk2a1 were recently linked to the human genetic disorder Okur-Chung neurodevelopmental syndrome (OCNDS). Consistent with the role of CSNK2A1 in cilium stability, we find that expression of OCNDS-associated Csnk2a1 variants in wild-type cells causes ciliary structural defects. Our findings provide insights into mechanisms involved in ciliary length regulation, trafficking, and stability that in turn shed light on the significance of cilia instability in human disease. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Actin modulators; CSNK2A1; OCNDS; Primary cilia; TTBK2
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179821
作者单位	Department of Pharmacology and Cancer Biology, Duke University, School of Medicine, Durham, NC 27710, United States
推荐引用方式 GB/T 7714	Loukil A.,Barrington C.,Goetz S.C.. A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability[J],2021,118(16).
APA	Loukil A.,Barrington C.,&Goetz S.C..(2021).A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Loukil A.,et al."A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).