HEATR2 plays a conserved role in assembly of the ciliary motile apparatus.
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 h...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-09-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC4168999?pdf=render |
id |
doaj-221a47d3cc01479e8e83de40453586ea |
---|---|
record_format |
Article |
spelling |
doaj-221a47d3cc01479e8e83de40453586ea2020-11-25T00:58:14ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-09-01109e100457710.1371/journal.pgen.1004577HEATR2 plays a conserved role in assembly of the ciliary motile apparatus.Christine P DiggleDaniel J MooreGirish MaliPetra zur LageAouatef Ait-LounisMiriam SchmidtsAmelia ShoemarkAmaya Garcia MunozMihail R HalachevPhilippe GautierPatricia L YeyatiDavid T BonthronIan M CarrBruce HaywardAlexander F MarkhamJilly E HopeAlex von KriegsheimHannah M MitchisonIan J JacksonBénédicte DurandWalter ReithEamonn SheridanAndrew P JarmanPleasantine MillCilia 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.http://europepmc.org/articles/PMC4168999?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine P Diggle Daniel J Moore Girish Mali Petra zur Lage Aouatef Ait-Lounis Miriam Schmidts Amelia Shoemark Amaya Garcia Munoz Mihail R Halachev Philippe Gautier Patricia L Yeyati David T Bonthron Ian M Carr Bruce Hayward Alexander F Markham Jilly E Hope Alex von Kriegsheim Hannah M Mitchison Ian J Jackson Bénédicte Durand Walter Reith Eamonn Sheridan Andrew P Jarman Pleasantine Mill |
spellingShingle |
Christine P Diggle Daniel J Moore Girish Mali Petra zur Lage Aouatef Ait-Lounis Miriam Schmidts Amelia Shoemark Amaya Garcia Munoz Mihail R Halachev Philippe Gautier Patricia L Yeyati David T Bonthron Ian M Carr Bruce Hayward Alexander F Markham Jilly E Hope Alex von Kriegsheim Hannah M Mitchison Ian J Jackson Bénédicte Durand Walter Reith Eamonn Sheridan Andrew P Jarman Pleasantine Mill HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. PLoS Genetics |
author_facet |
Christine P Diggle Daniel J Moore Girish Mali Petra zur Lage Aouatef Ait-Lounis Miriam Schmidts Amelia Shoemark Amaya Garcia Munoz Mihail R Halachev Philippe Gautier Patricia L Yeyati David T Bonthron Ian M Carr Bruce Hayward Alexander F Markham Jilly E Hope Alex von Kriegsheim Hannah M Mitchison Ian J Jackson Bénédicte Durand Walter Reith Eamonn Sheridan Andrew P Jarman Pleasantine Mill |
author_sort |
Christine P Diggle |
title |
HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. |
title_short |
HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. |
title_full |
HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. |
title_fullStr |
HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. |
title_full_unstemmed |
HEATR2 plays a conserved role in assembly of the ciliary motile apparatus. |
title_sort |
heatr2 plays a conserved role in assembly of the ciliary motile apparatus. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2014-09-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4168999?pdf=render |
work_keys_str_mv |
AT christinepdiggle heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT danieljmoore heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT girishmali heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT petrazurlage heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT aouatefaitlounis heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT miriamschmidts heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT ameliashoemark heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT amayagarciamunoz heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT mihailrhalachev heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT philippegautier heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT patricialyeyati heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT davidtbonthron heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT ianmcarr heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT brucehayward heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT alexanderfmarkham heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT jillyehope heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT alexvonkriegsheim heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT hannahmmitchison heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT ianjjackson heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT benedictedurand heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT walterreith heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT eamonnsheridan heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT andrewpjarman heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus AT pleasantinemill heatr2playsaconservedroleinassemblyoftheciliarymotileapparatus |
_version_ |
1725220927238569984 |