Nucleoporins are evolutionary conserved proteins mainly involved in the constitution of the nuclear pores and trafficking between the nucleus and cytoplasm, but are also increasingly viewed as main actors in chromatin dynamics and intra-nuclear mitotic events. Here, we determined the cellular localization of the nucleoporin Mlp2 in the 'divergent' eukaryotes Leishmania major and Trypanosoma brucei. In both protozoa, Mlp2 displayed an atypical localization for a nucleoporin, essentially intranuclear, and preferentially in the periphery of the nucleolus during interphase; moreover, it relocated at the mitotic spindle poles during mitosis. In T. brucei, where most centromeres have been identified, TbMlp2 was found adjacent to the centromeric sequences, as well as to a recently described unconventional kinetochore protein, in the periphery of the nucleolus, during interphase and from the end of anaphase onwards. TbMlp2 and the centromeres/kinetochores exhibited a differential migration towards the poles during mitosis. RNAi knockdown of TbMlp2 disrupted the mitotic distribution of chromosomes, leading to a surprisingly well-tolerated aneuploidy. In addition, diploidy was restored in a complementation assay where LmMlp2, the orthologue of TbMlp2 in Leishmania, was expressed in TbMlp2-RNAi-knockdown parasites. Taken together, our results demonstrate that Mlp2 is involved in the distribution of chromosomes during mitosis in trypanosomatids.
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http://dx.doi.org/10.1093/nar/gkv056 | DOI Listing |
Mol Biol Cell
November 2024
Institute of Biochemistry, ETH Zurich, Zurich 8092, Switzerland.
Nuclear pore complexes (NPCs) mediate all traffic between the nucleus and the cytoplasm and are among the most stable protein assemblies in cells. Budding yeast cells carry two variants of NPCs which differ in the presence or absence of the nuclear basket proteins Mlp1, Mlp2, and Pml39. The binding of these basket proteins occurs very late in NPC assembly and Mlp-positive NPCs are excluded from the region of the nuclear envelope that borders the nucleolus.
View Article and Find Full Text PDFJ Cell Biol
September 2023
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
The nuclear pore complex (NPC) physically interacts with chromatin and regulates gene expression. The Saccharomyces cerevisiae inner ring nucleoporin Nup170 has been implicated in chromatin organization and the maintenance of gene silencing in subtelomeric regions. To gain insight into how Nup170 regulates this process, we used protein-protein interactions, genetic interactions, and transcriptome correlation analyses to identify the Ctf18-RFC complex, an alternative proliferating cell nuclear antigen (PCNA) loader, as a facilitator of the gene regulatory functions of Nup170.
View Article and Find Full Text PDFJ Parasit Dis
December 2022
Parasite Immunology Lab, Microbiology Department, Indian Council of Medical Research (ICMR)-Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Patna, Bihar 800007 India.
Unlabelled: As an ailment, leishmaniasis is still an incessant challenge in neglected tropical diseases and neglected infections of poverty worldwide. At present, the diagnosis and treatment to combat tropical infections are not substantial remedies and require advanced & specific research. Therefore, there is a need for a potential novel target to overcome established medicament modalities' limitations in pathogenicity.
View Article and Find Full Text PDFPLoS Genet
November 2021
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
The robust proliferation of cancer cells requires vastly elevated levels of protein synthesis, which relies on a steady supply of aminoacylated tRNAs. Delivery of tRNAs to the cytoplasm is a highly regulated process, but the machinery for tRNA nuclear export is not fully elucidated. In this study, using a live cell imaging strategy that visualizes nascent transcripts from a specific tRNA gene in yeast, we identified the nuclear basket proteins Mlp1 and Mlp2, two homologs of the human TPR protein, as regulators of tRNA export.
View Article and Find Full Text PDFNucleic Acids Res
April 2015
Laboratory of Parasitology-Mycology, Faculty of Medicine, University Montpellier 1, Montpellier F34090, France CNRS 5290-IRD 224-University Montpellier 1&2 (UMR 'MiVEGEC'), Montpellier F34090, France.
Nucleoporins are evolutionary conserved proteins mainly involved in the constitution of the nuclear pores and trafficking between the nucleus and cytoplasm, but are also increasingly viewed as main actors in chromatin dynamics and intra-nuclear mitotic events. Here, we determined the cellular localization of the nucleoporin Mlp2 in the 'divergent' eukaryotes Leishmania major and Trypanosoma brucei. In both protozoa, Mlp2 displayed an atypical localization for a nucleoporin, essentially intranuclear, and preferentially in the periphery of the nucleolus during interphase; moreover, it relocated at the mitotic spindle poles during mitosis.
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