Impact of Leishmania infection on host macrophage nuclear physiology and nucleopore complex integrity

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 mole...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2015-03, Vol.11 (3), p.e1004776-e1004776
Main Authors: Isnard, Amandine, Christian, Jan G, Kodiha, Mohamed, Stochaj, Ursula, McMaster, W Robert, Olivier, Martin
Format: Article
Language:English
Subjects:
Animals
Cell Line, Transformed
Datasets
Experiments
Gene expression
Health aspects
Host-parasite relationships
Identification and classification
Infections
Leishmania - genetics
Leishmania - metabolism
Leishmaniasis
Leishmaniasis - genetics
Leishmaniasis - metabolism
Macrophages
Macrophages - metabolism
Macrophages - parasitology
Mass spectrometry
Metabolism
Metalloendopeptidases - genetics
Metalloendopeptidases - metabolism
Mice
Microscopy
NF-kappa B - genetics
NF-kappa B - metabolism
Nuclear Pore - genetics
Nuclear Pore - metabolism
Nuclear Pore Complex Proteins - genetics
Nuclear Pore Complex Proteins - metabolism
Parasites
Parasitic diseases
Physiological aspects
Physiology
Proteins
Scientific imaging
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004776