The nuclear basket nucleoporin MLP1 is required to maintain nuclear integrity, and mitotic fidelity in Trypanosoma...

Trypanosoma brucei, a divergent eukaryote parasite, is responsible for neglected tropical diseases in humans and animals, specifically sleeping sickness or human African trypanosomiasis and nagana. Beyond its scientific significance, a comprehensive understanding of its biology has substantial medical and economical implications. Nuclear pore complexes (NPCs) are large multiprotein channels embedded in the nuclear envelope that regulate nucleocytoplasmic transport. In addition to this critical function, NPCs are involved in essential nuclear processes such as chromosome segregation, transcription, and cytokinesis. This study demonstrates that Myosin-like protein-1 (MLP1) localizes to the nuclear basket of NPCs in T. brucei. Silencing of TbMLP1 by RNA interference in T. brucei procyclic cells resulted in severe growth, significant impairment of messenger RNA export, disorganization of nuclear structure, and marked genomic instability. Flow cytometry and fluorescence in situ hybridization (FISH) analyses revealed abnormal DNA content and a reduction in disomic cells, alongside an increase in monosomic, trisomic, and polysomic cells, indicating intolerable aneuploidy detrimental to cell viability. Together, these findings demonstrate that TbMLP1 links NPC function to multiple key cellular pathways. This research provides new insights into the mechanisms that maintain nuclear architecture, preserve nuclear envelope morphology, ensure genome stability, and faithful chromosome segregation, and support appropriat kinetochore distribution and mitotic spindle organization.