title: Induction of Ran GTP drives ciliogenesis.
abstract: The small GTPase Ran and the importin proteins regulate nucleocytoplasmic transport. New evidence suggests that Ran GTP and the importins are also involved in conveying proteins into cilia. In this study, we find that Ran GTP accumulation at the basal bodies is coordinated with the initiation of ciliogenesis. The Ran-binding protein 1 (RanBP1), which indirectly accelerates Ran GTP → Ran GDP hydrolysis and promotes the dissociation of the Ran/importin complex, also localizes to basal bodies and cilia. To confirm the crucial link between Ran GTP and ciliogenesis, we manipulated the levels of RanBP1 and determined the effects on Ran GTP and primary cilia formation. We discovered that RanBP1 knockdown results in an increased concentration of Ran GTP at basal bodies, leading to ciliogenesis. In contrast, overexpression of RanBP1 antagonizes primary cilia formation. Furthermore, we demonstrate that RanBP1 knockdown disrupts the proper localization of KIF17, a kinesin-2 motor, at the distal tips of primary cilia in Madin-Darby canine kidney cells. Our studies illuminate a new function for Ran GTP in stimulating cilia formation and reinforce the notion that Ran GTP and the importins play key roles in ciliogenesis and ciliary protein transport.
authors: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors: Shuling
authors: S
authors: Fan
authors: Eileen L
authors: EL
authors: Whiteman
authors: Toby W
authors: TW
authors: Hurd
authors: Jeremy C
authors: JC
authors: McIntyre
authors: John F
authors: JF
authors: Dishinger
authors: Chia Jen
authors: CJ
authors: Liu
authors: Jeffrey R
authors: JR
authors: Martens
authors: Kristen J
authors: KJ
authors: Verhey
authors: Uma
authors: U
authors: Sajjan
authors: Ben
authors: B
authors: Margolis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C409642:KIF17 protein, mouse; D009687:Nuclear Proteins; C091775:ran-binding protein 1; D016547:Kinesins; D020931:ran GTP-Binding Protein