SUMOylation of the small GTPase ARL-13 helps target signaling receptors into primary cilia, Li et al. reveal.

Primary cilia are microtubule-based membrane protrusions that serve as hubs for multiple signaling pathways. In C. elegans, ARL-13 promotes cilia assembly by coordinating intraflagellar transport along ciliary microtubules, and the GTPase is also required for the correct localization of signaling receptors to the ciliary membrane.

In a yeast two-hybrid screen for ARL-13 binding partners, Li et al. identified UBC-9, an enzyme that conjugates the small, ubiquitin-like modifier SUMO onto target proteins. UBC-9 colocalized with ARL-13 in primary cilia and SUMOylated the GTPase near its C terminus. A non-SUMOylatable ARL-13 mutant localized to cilia and restored ciliogenesis in worms lacking wild-type ARL-13. But the rescued cilia lacked membrane proteins like the mechanosensor polycystin-2, indicating that ARL-13 SUMOylation is required for the proper ciliary localization of signaling receptors. A constitutively SUMOylated version of ARL-13 successfully restored both ciliogenesis and receptor targeting.

The human homologue of ARL-13, ARL13B, is mutated in the ciliopathy Joubert syndrome. ARL13B was also SUMOylated by UBC9, and this modification was required for the ciliary localization of human polycystin-2. Because polycystin-2 is mutated in polycystic kidney disease, Li et al.'s findings may explain why Joubert syndrome patients have cystic kidneys. Mislocalization of other signaling proteins may underlie additional symptoms associated with the disease. Senior author Jinghua Hu now wants to investigate how SUMOylation regulates ARL-13's function in ciliary targeting. One possibility is that SUMOylation allows ARL-13 to bind an adaptor that links the GTPase to different receptors.

et al
J. Cell Biol.

Author notes

Text by Ben Short