GTP-binding of ARL-3 is activated by ARL-13 as a GEF and stabilized by UNC-119

Qing Zhang, Yan Li, Yuxia Zhang, Vicente Torres, Peter C Harris, Kun Ling, Jinghua Hu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Primary cilia are sensory organelles indispensable for organogenesis and tissue pattern formation. Ciliopathy small GTPase ARLs are proposed as prominent ciliary switches, which when disrupted result in dysfunctional cilia, yet how ARLs are activated remain elusive. Here, we discover a novel small GTPase functional module, which contains ARL-3, ARL-13, and UNC-119, localizes near the poorly understood inversin (InV)-like compartment in C. elegans. ARL-13 acts synergistically with UNC-119, but antagonistically with ARL-3, in regulating ciliogenesis. We demonstrate that ARL-3 is a unique small GTPase with unusual high intrinsic GDP release but low intrinsic GTP binding rate. Importantly, ARL-13 acts as a nucleotide exchange factor (GEF) of ARL-3, while UNC-119 can stabilize the GTP binding of ARL-3. We further show that excess inactivated ARL-3 compromises ciliogenesis. The findings reveal a novel mechanism that one ciliopathy GTPase ARL-13, as a GEF, coordinates with UNC-119, which may act as a GTP-binding stabilizing factor, to properly activate another GTPase ARL-3 in cilia, a regulatory process indispensable for ciliogenesis.

Original languageEnglish (US)
Article number24534
JournalScientific Reports
Volume6
DOIs
StatePublished - Apr 22 2016

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Monomeric GTP-Binding Proteins
Cilia
Guanosine Triphosphate
GTP Phosphohydrolases
Organogenesis
Organelles
Nucleotides
Ciliopathies

ASJC Scopus subject areas

  • General

Cite this

GTP-binding of ARL-3 is activated by ARL-13 as a GEF and stabilized by UNC-119. / Zhang, Qing; Li, Yan; Zhang, Yuxia; Torres, Vicente; Harris, Peter C; Ling, Kun; Hu, Jinghua.

In: Scientific Reports, Vol. 6, 24534, 22.04.2016.

Research output: Contribution to journalArticle

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abstract = "Primary cilia are sensory organelles indispensable for organogenesis and tissue pattern formation. Ciliopathy small GTPase ARLs are proposed as prominent ciliary switches, which when disrupted result in dysfunctional cilia, yet how ARLs are activated remain elusive. Here, we discover a novel small GTPase functional module, which contains ARL-3, ARL-13, and UNC-119, localizes near the poorly understood inversin (InV)-like compartment in C. elegans. ARL-13 acts synergistically with UNC-119, but antagonistically with ARL-3, in regulating ciliogenesis. We demonstrate that ARL-3 is a unique small GTPase with unusual high intrinsic GDP release but low intrinsic GTP binding rate. Importantly, ARL-13 acts as a nucleotide exchange factor (GEF) of ARL-3, while UNC-119 can stabilize the GTP binding of ARL-3. We further show that excess inactivated ARL-3 compromises ciliogenesis. The findings reveal a novel mechanism that one ciliopathy GTPase ARL-13, as a GEF, coordinates with UNC-119, which may act as a GTP-binding stabilizing factor, to properly activate another GTPase ARL-3 in cilia, a regulatory process indispensable for ciliogenesis.",
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AU - Li, Yan

AU - Zhang, Yuxia

AU - Torres, Vicente

AU - Harris, Peter C

AU - Ling, Kun

AU - Hu, Jinghua

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