title: Dopamine receptors reveal an essential role of IFT-B, KIF17, and Rab23 in delivering specific receptors to primary cilia.
abstract: Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane, but how this occurs remains poorly understood. In this study, we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanism requiring the receptor cytoplasmic tail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17. This targeting mechanism critically depends on Rab23, a small guanine nucleotide binding protein that has important effects on physiological signaling from cilia but was not known previously to be essential for ciliary delivery of any cargo. Depleting Rab23 prevents dopamine receptors from accessing the ciliary membrane. Conversely, fusion of Rab23 to a non-ciliary receptor is sufficient to drive robust, nucleotide-dependent mis-localization to the ciliary membrane. Dopamine receptors thus reveal a previously unrecognized mechanism of ciliary receptor targeting and functional role of Rab23 in promoting this process.
authors.affiliation: Program in Cell Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Alison
authors.initials: A
authors.lastname: Leaf
authors.affiliation: Program in Cell Biology, University of California, San Francisco, San Francisco, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Von Zastrow
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002923:Cilia / Q000502:physiology*; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D011954:Receptors, Dopamine / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C409642:KIF17 protein, mouse; D011954:Receptors, Dopamine; C431746:Rab23 protein, mouse; D016547:Kinesins; D020691:rab GTP-Binding Proteins
keywords: G protein-coupled receptor; cell biology; cilia; human; membrane traffic; mouse; signaling