Figure 5 Model of GSF-Cargo Release in Cilia with WT ARL3 versus p.Arg149 ARL3 Missense Variants
ARL13B assists ARL3 in cilia to exchange its bound GDP to GTP. The specific localization of ARL13B in the cilia creates a high concentration of ARL3-GTP. ARL3-GTP in turn can release the cargo bound to its cognate GSF, resulting in ciliary localization. Missense variants of ARL3 (including p.Arg149His and p.Arg149Cys) are not able to interact with ARL13B, and the ARL3GTP concentration is therefore low in the cilia, resulting in inefficient release of GSF cargo in the cilia.