The docking of kinesins, KIF5B and KIF5C, to Ran-binding protein 2 (RanBP2) is mediated via a novel RanBP2 domain

The Ran-binding protein 2 (RanBP2) is a vertebrate mosaic protein composed of four interspersed RanGTPase binding domains (RBDs), a variable and speci es-specific zinc finger cluster domain, leucine-rich, cyclophilin, and cycl ophilin-like (CLD) domains. Functional mapping of RanBP2 showed that the do mains, zinc finger and CLD, between RBD1 and RBD2, and RBD3 and RBD4, respe ctively, associate specifically with the nuclear export receptor, CRM1/expo rtin-1, and components of the 19 S regulatory particle of the 26 S proteaso me. Now, we report the mapping of a novel RanBP2 domain located between RBD 2 and RBD3, which is also conserved in the partially duplicated isoform Ran BP2L1. Yet, this domain leads to the neuronal association of only RanBP2 wi th two kinesin microtubule-based motor proteins, KIF5B and KIF5C. These kin esins associate directly in vitro and in vivo with RanBP2. Moreover, the ki nesin light chain and RanGTPase are part of this RanBP2 macroassembly compl ex. These data provide evidence of a specific docking site in RanBP2 for KI F5B and KIF5C. A model emerges whereby RanBP2 acts as a selective signal in tegrator of nuclear and cytoplasmic trafficking pathways in neurons.