Academic Journal
KDM3A coordinates actin dynamics with intraflagellar transport to regulate cilia stability
| العنوان: | KDM3A coordinates actin dynamics with intraflagellar transport to regulate cilia stability |
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| المؤلفون: | Yeyati, Patricia L, Schiller, Rachel, Mali, Girish, Kasioulis, Ioannis, Kawamura, Akane, Adams, Ian R, Playfoot, Christopher, Gilbert, Nick, van Heyningen, Veronica, Wills, Jimi, von Kriegsheim, Alex, Finch, Andrew, Sakai, Juro, Schofield, Christopher J, Jackson, Ian J, Mill, Pleasantine |
| المصدر: | Yeyati , P L , Schiller , R , Mali , G , Kasioulis , I , Kawamura , A , Adams , I R , Playfoot , C , Gilbert , N , van Heyningen , V , Wills , J , von Kriegsheim , A , Finch , A , Sakai , J , Schofield , C J , Jackson , I J & Mill , P 2017 , ' KDM3A coordinates actin dynamics with intraflagellar transport to regulate cilia stability ' , The Journal of cell biology , vol. 216 , no. 4 , pp. 999-1013 .... |
| سنة النشر: | 2017 |
| المجموعة: | University of Bristol: Bristol Reserach |
| مصطلحات موضوعية: | Actins/metabolism, Animals, Biological Transport/physiology, Cell Line, Cilia/metabolism, Flagella/metabolism, Gene Expression/physiology, Histone Demethylases/metabolism, Humans, Jumonji Domain-Containing Histone Demethylases/metabolism, Mice, Morphogenesis/physiology, Mutation/physiology, Phenotype |
| الوصف: | Cilia assembly and disassembly are coupled to actin dynamics, ensuring a coherent cellular response during environmental change. How these processes are integrated remains undefined. The histone lysine demethylase KDM3A plays important roles in organismal homeostasis. Loss-of-function mouse models of Kdm3a phenocopy features associated with human ciliopathies, whereas human somatic mutations correlate with poor cancer prognosis. We demonstrate that absence of KDM3A facilitates ciliogenesis, but these resulting cilia have an abnormally wide range of axonemal lengths, delaying disassembly and accumulating intraflagellar transport (IFT) proteins. KDM3A plays a dual role by regulating actin gene expression and binding to the actin cytoskeleton, creating a responsive "actin gate" that involves ARP2/3 activity and IFT. Promoting actin filament formation rescues KDM3A mutant ciliary defects. Conversely, the simultaneous depolymerization of actin networks and IFT overexpression mimics the abnormal ciliary traits of KDM3A mutants. KDM3A is thus a negative regulator of ciliogenesis required for the controlled recruitment of IFT proteins into cilia through the modulation of actin dynamics. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://research-information.bris.ac.uk/en/publications/99296957-df16-4da2-9a4a-5d8e37197796 |
| DOI: | 10.1083/jcb.201607032 |
| الاتاحة: | https://hdl.handle.net/1983/99296957-df16-4da2-9a4a-5d8e37197796 https://research-information.bris.ac.uk/en/publications/99296957-df16-4da2-9a4a-5d8e37197796 https://doi.org/10.1083/jcb.201607032 https://research-information.bris.ac.uk/ws/files/311325321/jcb_201607032.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9061C1FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1083/jcb.201607032 |
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