Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis.
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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The Journal of clinical investigation
2026
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| author | He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing |
| author_facet | He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing |
| collection | PubMed - marine biology |
| contents | Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis. He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing Humans Protein Processing, Post-Translational Cilia Axoneme Membrane Proteins Ciliopathies Microtubules Retina Cerebellum Kidney Diseases, Cystic Abnormalities, Multiple Microtubule-Associated Proteins Animals Multiprotein Complexes HEK293 Cells Cerebellar Diseases Encephalocele Centrioles Proteins Eye Abnormalities Ciliary dysfunction results in multiorgan developmental diseases, collectively known as ciliopathies. The B9D1-B9D2-MKS1protein complex maintains the gatekeeper function at the ciliary transition zone (TZ). However, the function of B9 proteins and the mechanisms underlying why different variants in the same B9 gene cause different ciliopathies are not fully understood. Here, we investigated the function of B9 proteins and revealed 2 critical functions. First, the B9 complex interacted with and anchored TMEM67 to the TZ membrane. Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia. Second, B9 proteins localized to centrioles prior to ciliogenesis, where they facilitated the initiation of ciliogenesis. In addition, we identified B9D2 variants in a cohort of patients with Joubert syndrome. We found that Joubert syndrome-associated B9D2 variants primarily affected axonemal microtubule modifications without disrupting ciliogenesis, whereas the Meckel syndrome-associated B9D2 variant disrupted both ciliogenesis and axonemal microtubule modifications. Thus, besides its role as a gatekeeper for ciliary membrane proteins, the B9 complex also controls axonemal microtubule posttranslational modifications and early stages of ciliogenesis, providing insights into the distinct pathologies arising from different variants of the same gene. |
| format | Artículo científico |
| id | pubmed_41165761 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | The Journal of clinical investigation |
| record_format | pubmed |
| spellingShingle | Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis. He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing Humans Protein Processing, Post-Translational Cilia Axoneme Membrane Proteins Ciliopathies Microtubules Retina Cerebellum Kidney Diseases, Cystic Abnormalities, Multiple Microtubule-Associated Proteins Animals Multiprotein Complexes HEK293 Cells Cerebellar Diseases Encephalocele Centrioles Proteins Eye Abnormalities Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis. He, Ruida Li, Yan Jin, Minjun Jiao, Huike Shen, Yue Han, Qize Pan, Xilang Wang, Suning Lin, Zaisheng Li, Jingshi Lu, Chao Meng, Dan Cao, Zongfu Shang, Qing Lv, Nan Wan, Kai Gao, Huafang Ma, Xu Yin, Haiyan Chang, Haishuang Wang, Liang Luo, Minna Pan, Junmin Zhao, Chengtian Cao, Muqing Humans Protein Processing, Post-Translational Cilia Axoneme Membrane Proteins Ciliopathies Microtubules Retina Cerebellum Kidney Diseases, Cystic Abnormalities, Multiple Microtubule-Associated Proteins Animals Multiprotein Complexes HEK293 Cells Cerebellar Diseases Encephalocele Centrioles Proteins Eye Abnormalities Ciliary dysfunction results in multiorgan developmental diseases, collectively known as ciliopathies. The B9D1-B9D2-MKS1protein complex maintains the gatekeeper function at the ciliary transition zone (TZ). However, the function of B9 proteins and the mechanisms underlying why different variants in the same B9 gene cause different ciliopathies are not fully understood. Here, we investigated the function of B9 proteins and revealed 2 critical functions. First, the B9 complex interacted with and anchored TMEM67 to the TZ membrane. Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia. Second, B9 proteins localized to centrioles prior to ciliogenesis, where they facilitated the initiation of ciliogenesis. In addition, we identified B9D2 variants in a cohort of patients with Joubert syndrome. We found that Joubert syndrome-associated B9D2 variants primarily affected axonemal microtubule modifications without disrupting ciliogenesis, whereas the Meckel syndrome-associated B9D2 variant disrupted both ciliogenesis and axonemal microtubule modifications. Thus, besides its role as a gatekeeper for ciliary membrane proteins, the B9 complex also controls axonemal microtubule posttranslational modifications and early stages of ciliogenesis, providing insights into the distinct pathologies arising from different variants of the same gene. |
| title | Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis. |
| topic | Humans Protein Processing, Post-Translational Cilia Axoneme Membrane Proteins Ciliopathies Microtubules Retina Cerebellum Kidney Diseases, Cystic Abnormalities, Multiple Microtubule-Associated Proteins Animals Multiprotein Complexes HEK293 Cells Cerebellar Diseases Encephalocele Centrioles Proteins Eye Abnormalities |
| url | https://pubmed.ncbi.nlm.nih.gov/41165761/ |