title: The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain.
abstract: The Ran-binding protein 2 (RanBP2) is a vertebrate mosaic protein composed of four interspersed RanGTPase binding domains (RBDs), a variable and species-specific zinc finger cluster domain, leucine-rich, cyclophilin, and cyclophilin-like (CLD) domains. Functional mapping of RanBP2 showed that the domains, zinc finger and CLD, between RBD1 and RBD2, and RBD3 and RBD4, respectively, associate specifically with the nuclear export receptor, CRM1/exportin-1, and components of the 19 S regulatory particle of the 26 S proteasome. Now, we report the mapping of a novel RanBP2 domain located between RBD2 and RBD3, which is also conserved in the partially duplicated isoform RanBP2L1. Yet, this domain leads to the neuronal association of only RanBP2 with two kinesin microtubule-based motor proteins, KIF5B and KIF5C. These kinesins associate directly in vitro and in vivo with RanBP2. Moreover, the kinesin light chain and RanGTPase are part of this RanBP2 macroassembly complex. These data provide evidence of a specific docking site in RanBP2 for KIF5B and KIF5C. A model emerges whereby RanBP2 acts as a selective signal integrator of nuclear and cytoplasmic trafficking pathways in neurons.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: B B
authors.initials: BB
authors.lastname: Singh
authors.forename: A
authors.initials: A
authors.lastname: Aslanukov
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: P A
authors.initials: PA
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D001923:Brain Chemistry; D002417:Cattle; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones; D008970:Molecular Weight; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D012160:Retina / Q000737:chemistry
chemical_list: C411575:KIFC5 protein, mouse; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2