Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00473106" target="_blank" >RIV/68378050:_____/16:00473106 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1073/pnas.1604258113" target="_blank" >http://dx.doi.org/10.1073/pnas.1604258113</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.1604258113" target="_blank" >10.1073/pnas.1604258113</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

Popis výsledku v původním jazyce

The transition zone (TZ) of eukaryotic cilia and flagella is a structural intermediate between the basal body and the axoneme that regulates ciliary traffic. Mutations in genes encoding TZ proteins (TZPs) cause human inherited diseases (ciliopathies). Here, we use the trypanosome to identify TZ components and localize them to TZ subdomains, showing that the Bardet-Biedl syndrome complex (BBSome) is more distal in the TZ than the Meckel syndrome (MKS) complex. Several of the TZPs identified here have human orthologs. Functional analysis shows essential roles for TZPs in motility, in building the axoneme central pair apparatus and in flagellum biogenesis. Analysis using RNAi and HaloTag fusion protein approaches reveals that most TZPs (including the MKS ciliopathy complex) show long-term stable association with the TZ, whereas the BBSome is dynamic. We propose that some Bardet-Biedl syndrome and MKS pleiotropy may be caused by mutations that impact TZP complex dynamics.

Název v anglickém jazyce

Cilium transition zone proteome reveals compartmentalization and differential dynamics of ciliopathy complexes

Popis výsledku anglicky

The transition zone (TZ) of eukaryotic cilia and flagella is a structural intermediate between the basal body and the axoneme that regulates ciliary traffic. Mutations in genes encoding TZ proteins (TZPs) cause human inherited diseases (ciliopathies). Here, we use the trypanosome to identify TZ components and localize them to TZ subdomains, showing that the Bardet-Biedl syndrome complex (BBSome) is more distal in the TZ than the Meckel syndrome (MKS) complex. Several of the TZPs identified here have human orthologs. Functional analysis shows essential roles for TZPs in motility, in building the axoneme central pair apparatus and in flagellum biogenesis. Analysis using RNAi and HaloTag fusion protein approaches reveals that most TZPs (including the MKS ciliopathy complex) show long-term stable association with the TZ, whereas the BBSome is dynamic. We propose that some Bardet-Biedl syndrome and MKS pleiotropy may be caused by mutations that impact TZP complex dynamics.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

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Svazek periodika

113

Číslo periodika v rámci svazku

35

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

"E5135"-"E5143"

Kód UT WoS článku

000383090700009

EID výsledku v databázi Scopus

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