title: A role for Rab23 in the trafficking of Kif17 to the primary cilium.
abstract: The small GTPase Rab23 is an antagonist of sonic hedgehog (Shh) signaling during mouse development. Given that modulation of Shh signaling depends on the normal functioning of the primary cilium, and overexpression of Evi5L, a putative Rab23 GTPase-activating protein (GAP), leads to reduced ciliogenesis, Rab23 could have a role at the primary cilium. Here, we found that wild-type Rab23 and the constitutively active Rab23 Q68L mutant were enriched at the primary cilium. Therefore, we tested the role of Rab23 in the ciliary targeting of known cargoes and found that ciliary localization of the kinesin-2 motor protein Kif17 was disrupted in Rab23-depleted cells. Co-immunoprecipitation and affinity-binding studies revealed that Rab23 exists in a complex with Kif17 and importin β2 (the putative Kif17 ciliary import carrier), implying that Kif17 needs to bind to regulatory proteins like Rab23 for its ciliary transport. Although a ciliary-cytoplasmic gradient of nuclear Ran is necessary to regulate the ciliary transport of Kif17, Rab23 and Ran appear to have differing roles in regulating the ciliary entry of Kif17. Our findings have uncovered a hitherto unknown effector of Rab23 and demonstrate how Rab23 could mediate the transport of Kif17 to the primary cilium.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, 8 Medical Drive, 117597 Singapore.
authors.forename: Yi Shan
authors.initials: YS
authors.lastname: Lim
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, 8 Medical Drive, 117597 Singapore National University of Singapore Graduate School of Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456 Singapore bchtbl@nus.edu.sg.
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002923:Cilia / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics; D020690:GTPase-Activating Proteins; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D028961:beta Karyopherins / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C105043:Evi5 protein, mouse; D020690:GTPase-Activating Proteins; D053823:Hedgehog Proteins; C409642:KIF17 protein, mouse; C465570:Shh protein, mouse; D014157:Transcription Factors; D028961:beta Karyopherins; C431746:Rab23 protein, mouse; D016547:Kinesins; D020691:rab GTP-Binding Proteins
keywords: Importin β2; Kif17; Primary cilium; Rab23; Trafficking