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J. Cell Biol. 199 (4): 589-598

Copyright © 2012 by the Rockefeller University Press.

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SUMOylation of the small GTPase ARL-13 promotes ciliary targeting of sensory receptors

Yujie Li1, Qing Zhang1, Qing Wei1, Yuxia Zhang1, Kun Ling1,3, , and Jinghua Hu1,2,3

1 Department of Biochemistry and Molecular Biology, 2 Division of Nephrology and Hypertension, and 3 Department of Internal Medicine, Mayo Translational Polycystic Kidney Disease (PKD) Center, Mayo Clinic, Rochester, MN 55905

Correspondence to Jinghua Hu: hu.jinghua{at}mayo.edu

Abstract: Primary cilia serve as cellular antenna for various sensory signaling pathways. However, how the sensory receptors are properly targeted to the ciliary surface remains poorly understood. Here, we show that UBC-9, the sole E2 small ubiquitin-like modifier (SUMO)-conjugating enzyme, physically interacts with and SUMOylates the C terminus of small GTPase ARL-13, the worm orthologue of ARL13B that mutated in ciliopathy Joubert syndrome. Mutations that totally abolish the SUMOylation of ARL-13 do not affect its established role in ciliogenesis, but fail to regulate the proper ciliary targeting of various sensory receptors and consequently compromise the corresponding sensory functions. Conversely, constitutively SUMOylated ARL-13 fully rescues all ciliary defects of arl-13–null animals. Furthermore, SUMOylation modification of human ARL13B is required for the ciliary entry of polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease. Our data reveal a novel but conserved role for the SUMOylation modification of ciliary small GTPase ARL13B in specifically regulating the proper ciliary targeting of various sensory receptors.

Abbreviations: hTERT-RPE1, hTERT–immortalized retinal pigment epithelial cell line • IFT, intraflagellar transport • IMCD3, murine inner medullary collecting duct • JS, Joubert syndrome • PRD, proline-rich domain • SIM, SUMO interaction motif • SUMO, small ubiquitin-like modifier

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
ARL-13 SUMO wrestles receptors into cilia.
B. Short (2012)
J. Cell Biol. 199, 566
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