title: Inhibition of active nuclear transport is an intrinsic trigger of programmed cell death in trypanosomatids.
abstract: The link between nucleocytoplasmic transport and apoptosis remains controversial. Nucleocytoplasmic exchange of molecules seems indeed essential for the initiation and execution of the apoptotic programme; but inhibition of nuclear transport factors may also represent a powerful apoptotic trigger. The GTPase Ran (together with its partners), first discovered to be essential in nucleocytoplasmic transport, has multiple key functions in cell biology, and particularly in spindle assembly, kinetochore function and nuclear envelope assembly. Among the Ran partners studied, NTF2 appears to be solely involved in nucleocytoplasmic transport. Here, we localised Ran and several of its partners, RanBP1, CAS and NTF2, at the nuclear membrane in the trypanosomatid Leishmania major. Remarkably, these proteins fused to GFP decorated a perinuclear 'collar' of about 15 dots, colocalising at nuclear pore complexes with the homologue of nucleoporin Sec13. In the other trypanosomatid Trypanosoma brucei, RNAi knockdown of the expression of the corresponding genes resulted in an apoptosis-like phenomenon. These phenotypes show that Ran and its partners have a key function in trypanosomatids like they have in mammals. Our data, notably those about TbNTF2 RNAi, support the idea that active nucleocytoplasmic transport is not essential for the initiation and execution of apoptosis, and, rather, the impairment of this transport constitutes an intrinsic signal for triggering PCD.
authors.affiliation: University Montpellier 1, Laboratoire de Parasitologie-Mycologie, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Casanova
authors.forename: P
authors.initials: P
authors.lastname: Portalès
authors.forename: C
authors.initials: C
authors.lastname: Blaineau
authors.forename: L
authors.initials: L
authors.lastname: Crobu
authors.forename: P
authors.initials: P
authors.lastname: Bastien
authors.forename: M
authors.initials: M
authors.lastname: Pagès
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism*; D017125:Genes, Protozoan; D016678:Genome; D018320:Leishmania major / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000201:enzymology; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: C080324:GSP1 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D015800:Protozoan Proteins; C079620:SEC13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020559:Monomeric GTP-Binding Proteins; D020931:ran GTP-Binding Protein