title: RanBP1 governs spindle assembly by defining mitotic Ran-GTP production.
abstract: Accurate control of the Ras-related nuclear protein (Ran) GTPase cycle depends on the regulated activity of regulator of chromosome condensation 1 (RCC1), Ran's nucleotide exchange factor. RanBP1 has been characterized as a coactivator of the Ran GTPase-activating protein RanGAP1. RanBP1 can also form a stable complex with Ran and RCC1, although the dynamics and function of this complex remain poorly understood. Here, we show that formation of the heterotrimeric RCC1/Ran/RanBP1 complex in M phase Xenopus egg extracts controls both RCC1's enzymatic activity and partitioning between the chromatin-bound and soluble pools of RCC1. This mechanism is critical for spatial control of Ran-guanosine triphosphate (GTP) gradients that guide mitotic spindle assembly. Moreover, phosphorylation of RanBP1 drives changes in the dynamics of chromatin-bound RCC1 pools at the metaphase-anaphase transition. Our findings reveal an important mitotic role for RanBP1, controlling the spatial distribution and magnitude of mitotic Ran-GTP production and thereby ensuring accurate execution of Ran-dependent mitotic events.
authors.affiliation: Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael Shaofei
authors.initials: MS
authors.lastname: Zhang
authors.affiliation: Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Arnaoutov
authors.affiliation: Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: dassom@mail.nih.gov.
authors.forename: Mary
authors.initials: M
authors.lastname: Dasso
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000096:biosynthesis*; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D029867:Xenopus Proteins; C091775:ran-binding protein 1; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein