Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia
Abstract Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primar...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-86292-5 |
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| author | Jae Hee Jun Hwayeon Cha Je Yeong Ko Ho-Shik Kim Kyung Hyun Yoo Jong Hoon Park |
| author_facet | Jae Hee Jun Hwayeon Cha Je Yeong Ko Ho-Shik Kim Kyung Hyun Yoo Jong Hoon Park |
| author_sort | Jae Hee Jun |
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| description | Abstract Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary cilia regulation remains unclear. In this study, histone K (lysine) acetyltransferase 2 B (Kat2b) was identified as a novel regulator of primary cilia. Kat2b, which mainly regulates transcription as a p300/CBP associated factor, is localized to the cytosol, centrosome, and cilium basal body. In addition, basal Kat2b expression gradually increased during ciliogenesis. Kat2b regulates the rate of cilia assembly, particularly in the early stages, and loss of Kat2b reduces the recruitment of intraflagellar transport (IFT) components to the ciliary axoneme and impairs Hedgehog (Hh) signaling activation. In addition, Kat2b-knockout mice showed mild abnormalities and ciliary IFT defects in the kidneys. These results establish a link between acetylation regulated by Kat2b and its relevance to ciliary assembly and function. |
| format | Article |
| id | doaj-art-3593b02cec0c44ebaedc73a3deec60e7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-3593b02cec0c44ebaedc73a3deec60e72025-01-19T12:20:50ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-86292-5Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary ciliaJae Hee Jun0Hwayeon Cha1Je Yeong Ko2Ho-Shik Kim3Kyung Hyun Yoo4Jong Hoon Park5Department of Biological Science, Sookmyung Women’s UniversityDepartment of Biological Science, Sookmyung Women’s UniversityDepartment of Biological Science, Sookmyung Women’s UniversityDepartment of Biochemistry, College of Medicine, The Catholic University of KoreaDepartment of Biological Science, Sookmyung Women’s UniversityDepartment of Biological Science, Sookmyung Women’s UniversityAbstract Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary cilia regulation remains unclear. In this study, histone K (lysine) acetyltransferase 2 B (Kat2b) was identified as a novel regulator of primary cilia. Kat2b, which mainly regulates transcription as a p300/CBP associated factor, is localized to the cytosol, centrosome, and cilium basal body. In addition, basal Kat2b expression gradually increased during ciliogenesis. Kat2b regulates the rate of cilia assembly, particularly in the early stages, and loss of Kat2b reduces the recruitment of intraflagellar transport (IFT) components to the ciliary axoneme and impairs Hedgehog (Hh) signaling activation. In addition, Kat2b-knockout mice showed mild abnormalities and ciliary IFT defects in the kidneys. These results establish a link between acetylation regulated by Kat2b and its relevance to ciliary assembly and function.https://doi.org/10.1038/s41598-025-86292-5AcetylationCiliogenesisIntraflagellar transportKat2bPrimary cilia |
| spellingShingle | Jae Hee Jun Hwayeon Cha Je Yeong Ko Ho-Shik Kim Kyung Hyun Yoo Jong Hoon Park Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia Scientific Reports Acetylation Ciliogenesis Intraflagellar transport Kat2b Primary cilia |
| title | Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia |
| title_full | Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia |
| title_fullStr | Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia |
| title_full_unstemmed | Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia |
| title_short | Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia |
| title_sort | loss of kat2b impairs intraflagellar transport and the hedgehog signaling pathway in primary cilia |
| topic | Acetylation Ciliogenesis Intraflagellar transport Kat2b Primary cilia |
| url | https://doi.org/10.1038/s41598-025-86292-5 |
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