Author:
Kim Dong Yun,Sub Yu Jin,Kim Hye-Youn,Cho Kyeong Jee,Choi Won Il,Choi Yo Jun,Lee Min Goo,Hildebrandt Friedhelm,Gee Heon Yung
Abstract
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.
Funder
Ministry of Health & Welfare, Republic of Korea
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
4 articles.
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