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Lookup NU author(s): Professor Akane Kawamura
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 Yeyati et al. 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.
Author(s): Yeyati PL, Schiller R, Mali G, Kasioulis I, Kawamura A, Adams IR, Playfoot C, Gilbert N, van Heyningen V, Wills J, von Kriegsheim A, Finch A, Sakai J, Schofield CJ, Jackson IJ, Mill P
Publication type: Article
Publication status: Published
Journal: Journal of Cell Biology
Year: 2017
Volume: 216
Issue: 4
Pages: 999-1013
Print publication date: 03/04/2017
Online publication date: 28/02/2017
Acceptance date: 12/01/2017
Date deposited: 11/10/2019
ISSN (print): 0021-9525
ISSN (electronic): 1540-8140
Publisher: Rockefeller University Press
URL: https://doi.org/10.1083/jcb.201607032
DOI: 10.1083/jcb.201607032
PubMed id: 28246120
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