Leishmania donovani RAN-GTPase interacts at the nuclear rim with linker histone H1

Despina Smirlis (1) , Haralabia Boleti (1) , Maria Gaitanou (1) , Manuel Soto (2) , Ketty Soteriadou (1)

1 Institut Pasteur Hellénique
2 CBMSO - Centro de Biología Molecular Severo Ochoa [Madrid]

Ran-GTPase regulates multiple cellular processes such as nucleo-cytoplasmic transport, mitotic spindle assembly, nuclear envelope assembly, cell-cycle progression and the mitotic checkpoint. The leishmanial Ran protein contrary to its mammalian counterpart which is predominately nucleoplasmic is localised at the nuclear rim. The focus of this paper was to characterise the L.donovani Ran orthologue (LdRan) with emphasis on the Ran-histone association. LdRan was found to be developmentally regulated, expressed three times less in the amastigote stage. LdRan over-expression caused a growth defect linked to a delayed S-phase progression in promastigotes like 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-localise 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 localisation 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 other pathways than those documented for the metazoan Ran-core histone association.

Mots clés: Life Sciences

Domaines: Parasitologie

Despina Smirlis, Haralabia Boleti, Maria Gaitanou, Manuel Soto, Ketty Soteriadou. Leishmania donovani RAN-GTPase interacts at the nuclear rim with linker histone H1. Biochemical Journal, 2009, 424 (3), pp.367-374. ⟨10.1042/BJ20090576⟩. ⟨hal-00479187⟩