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LRRC6 regulates biogenesis of motile cilia by aiding FOXJ1 translocation into the nucleus

Authors
 Dong Yun Kim  ;  Yu Jin Sub  ;  Hye-Youn Kim  ;  Kyeong Jee Cho  ;  Won Il Choi  ;  Yo Jun Choi  ;  Min Goo Lee  ;  Friedhelm Hildebrandt  ;  Heon Yung Gee 
Citation
 CELL COMMUNICATION AND SIGNALING, Vol.21(1) : 142, 2023-06 
Journal Title
CELL COMMUNICATION AND SIGNALING
Issue Date
2023-06
MeSH
Animals ; Cilia* / metabolism ; Cytoskeletal Proteins / metabolism ; Dyneins* / genetics ; Dyneins* / metabolism ; Forkhead Transcription Factors* / metabolism ; Gene Expression Regulation ; Mice ; Mice, Knockout ; Proteins / genetics ; Proteomics
Keywords
FOXJ1 ; LRRC6 ; Motile cilia ; Nuclear translocation ; Primary ciliary dyskinesia
Abstract
Background: LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription.

Methods: We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings.

Results: The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor.

Conclusions: Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. Video Abstract
Files in This Item:
T202304162.pdf Download
DOI
10.1186/s12964-023-01135-y
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Yun(김동윤) ORCID logo https://orcid.org/0000-0002-2471-3385
Kim, Hye-Youn(김혜연) ORCID logo https://orcid.org/0000-0003-2090-6427
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195965
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