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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Main Authors: Jae Hee Jun, Hwayeon Cha, Je Yeong Ko, Ho-Shik Kim, Kyung Hyun Yoo, Jong Hoon Park
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
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
collection DOAJ
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.
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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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