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A critical role of perinuclear filamentous actin in spatial repositioning and mutually exclusive expression of virulence genes in malaria parasites.
- Source :
-
Cell host & microbe [Cell Host Microbe] 2011 Nov 17; Vol. 10 (5), pp. 451-63. - Publication Year :
- 2011
-
Abstract
- Many microbial pathogens, including the malaria parasite Plasmodium falciparum, vary surface protein expression to evade host immune responses. P. falciparium antigenic variation is linked to var gene family-encoded clonally variant surface protein expression. Mututally exclusive var gene expression is partially controlled by spatial positioning; silent genes are retained at distinct perinuclear sites and relocated to transcriptionally active locations for monoallelic expression. We show that var introns can control this process and that var intron addition relocalizes episomes from a random to a perinuclear position. This var intron-regulated nuclear tethering and repositioning is linked to an 18 bp nuclear protein-binding element that recruits an actin protein complex. Pharmacologically induced F-actin formation, which is restricted to the nuclear periphery, repositions intron-carrying episomes and var genes and disrupts mutually exclusive var gene expression. Thus, actin polymerization relocates var genes from a repressive to an active perinuclear compartment, which is crucial for P. falciparium phenotypic variation and pathogenesis.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Actins genetics
Cell Nucleus genetics
Gene Expression Regulation
Humans
Introns
Plasmids genetics
Plasmids metabolism
Plasmodium falciparum genetics
Protein Binding
Protein Transport
Protozoan Proteins genetics
Virulence Factors genetics
Actins metabolism
Cell Nucleus metabolism
Malaria, Falciparum parasitology
Plasmodium falciparum metabolism
Protozoan Proteins metabolism
Virulence Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1934-6069
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell host & microbe
- Publication Type :
- Academic Journal
- Accession number :
- 22100161
- Full Text :
- https://doi.org/10.1016/j.chom.2011.09.013