Ran-GTPase regulates multiple cellular processes such as nucleocytoplasmic transport, mitotic spindle assembly, nuclear envelope assembly, cell-cycle progression and the mitotic checkpoint. The leishmanial Ran protein, in contrast with its mammalian counterpart which is predominately nucleoplasmic, is localized at the nuclear rim. The aim of the present study was to characterize the LdRan (Leishmania donovani Ran) orthologue with an emphasis on the Ran–histone association. LdRan was found to be developmentally regulated, expressed 3-fold less in the amastigote stage. LdRan overexpression caused a growth defect linked to a delayed S-phase progression in promastigotes as for its mammalian counterpart. We report for the first time that Ran interacts with a linker histone, histone H1, in vitro and that the two proteins co-localize at the parasite nuclear rim. Interaction of Ran with core histones H3 and H4, creating in metazoans a chromosomal Ran-GTP gradient important for mitotic spindle assembly, is speculative in Leishmania spp., not only because this parasite undergoes a closed mitosis, but also because the main localization of LdRan is different from that of core histone H3. Interaction of Ran with the leishmanial linker histone H1 (LeishH1) suggests that this association maybe involved in modulation of pathways other than those documented for the metazoan Ran–core histone association.
Overexpression of Ran GTPase Components Regulating Nuclear Export, but not Mitotic Spindle Assembly, Marks Chromosome Instability and Poor Prognosis in Breast Cancer
