Impact of Leishmania Infection on Host Macrophage Nuclear Physiology and Nucleopore Complex Integrity

PLoS Pathogens

W. Robert McMaster¹  Mohamed Kodiha²  Ursula Stochaj²  Martin Olivier³  Amandine Isnard³  Jan G. Christian³ 

[1] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada;Department of Physiology, McGill University, Montréal, Quebec, Canada;Departments of Medicine and Microbiology & Immunology, The Research Institute of the McGill University Health Centre, McGill University, Montréal, Quebec, Canada

关键词: Leishmania;    Parasitic diseases;    Proteomic databases;    Macrophages;    Parasite physiology;    Sequence motif analysis;    Proteases;    Host cells;   

DOI  :  10.1371/journal.ppat.1004776

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The protease GP63 is an important virulence factor of Leishmania parasites. We previously showed that GP63 reaches the perinuclear area of host macrophages and that it directly modifies nuclear translocation of the transcription factors NF-κB and AP-1. Here we describe for the first time, using molecular biology and in-depth proteomic analyses, that GP63 alters the host macrophage nuclear envelope, and impacts on nuclear processes. Our results suggest that GP63 does not appear to use a classical nuclear localization signal common between Leishmania species for import, but degrades nucleoporins, and is responsible for nuclear transport alterations. In the nucleoplasm, GP63 activity accounts for the degradation and mislocalization of proteins involved amongst others in gene expression and in translation. Collectively, our data indicates that Leishmania infection strongly affects nuclear physiology, suggesting that targeting of nuclear physiology may be a strategy beneficial for virulent Leishmania parasites.

【 授权许可】

CC BY