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KDM3A coordinates actin dynamics with intraflagellar transport to regulate cilia stability

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.

Publication metadata

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


DOI: 10.1083/jcb.201607032

PubMed id: 28246120


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Funder referenceFunder name
Cancer Research UK
Wellcome Trust