Qing Zhang, Yan Li, Yuxia Zhang, Vicente E Torres, Peter C Harris, Kun Ling, Jinghua Hu
Scientific reports 2016 Apr 22Primary 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.
Qing Zhang, Yan Li, Yuxia Zhang, Vicente E Torres, Peter C Harris, Kun Ling, Jinghua Hu. GTP-binding of ARL-3 is activated by ARL-13 as a GEF and stabilized by UNC-119. Scientific reports. 2016 Apr 22;6:24534
PMID: 27102355
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