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HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus
Date Issued
2014-09-18
Date Available
2016-03-02T14:53:01Z
Abstract
Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme.
Sponsorship
Science Foundation Ireland
Other Sponsorship
BBSRC studentship
EGRS scholarship
CMVM studentship
Action Medical Research UK Clinical Training Fellowship
Dutch Kidney Foundation
Milena Carvajal Pro-Kartagener Foundation
Action Medical Research
Newlife Foundation for Disabled Children UK
Fondation pour la Recherche Médicale
ANR
SWISS National Science Foundation
Medical Research Council of Great Britain
Type of Material
Journal Article
Publisher
Public Library of Science
Journal
PLoS Genetics
Copyright (Published Version)
2014 the Authors
Subjects
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Name
HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus - INCOMPLETE.pdf
Size
4.45 MB
Format
Adobe PDF
Checksum (MD5)
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