title: SUMOylation of the small GTPase ARL-13 promotes ciliary targeting of sensory receptors.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Translational Polycystic Kidney Disease Center, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wei
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Ling
authors.forename: Jinghua
authors.initials: J
authors.lastname: Hu
mesh_terms: D020727:ADP-Ribosylation Factors / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D058207:Sumoylation; D050396:TRPP Cation Channels / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D020727:ADP-Ribosylation Factors; D029742:Caenorhabditis elegans Proteins; D020559:Monomeric GTP-Binding Proteins; D050396:TRPP Cation Channels; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; C550601:ARL-13 protein, C elegans; C530391:ARL13B protein, human