Pfsec13 is an unusual chromatin-associated nucleoporin of plasmodium falciparum that is essential for parasite proliferation in human erythrocytes

Dahan-Pasternak, N; Nasereddin, A; Kolevzon, N; Pe'er, M; Wong, W; Shinder, V; Turnbull, L; Whitchurch, CB; Elbaum, M; Gilberger, TW; Yavin, E; Baum, J; Dzikowski, R

Pfsec13 is an unusual chromatin-associated nucleoporin of plasmodium falciparum that is essential for parasite proliferation in human erythrocytes

Dahan-Pasternak, N Nasereddin, A Kolevzon, N Pe'er, M Wong, W Shinder, V Turnbull, L

Whitchurch, CB

Elbaum, M Gilberger, TW Yavin, E Baum, J Dzikowski, R

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Publication Type:: Journal Article
Citation:: Journal of Cell Science, 2013, 126 (14), pp. 3055 - 3069
Issue Date:: 2013-07-01

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Field	Value	Language
dc.contributor.author	Dahan-Pasternak, N	en_US
dc.contributor.author	Nasereddin, A	en_US
dc.contributor.author	Kolevzon, N	en_US
dc.contributor.author	Pe'er, M	en_US
dc.contributor.author	Wong, W	en_US
dc.contributor.author	Shinder, V	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.contributor.author	Elbaum, M	en_US
dc.contributor.author	Gilberger, TW	en_US
dc.contributor.author	Yavin, E	en_US
dc.contributor.author	Baum, J	en_US
dc.contributor.author	Dzikowski, R	en_US
dc.date.issued	2013-07-01	en_US
dc.identifier.citation	Journal of Cell Science, 2013, 126 (14), pp. 3055 - 3069	en_US
dc.identifier.issn	0021-9533	en_US
dc.identifier.uri	http://hdl.handle.net/10453/26514
dc.description.abstract	In Plasmodium falciparum, the deadliest form of human malaria, the nuclear periphery has drawn much attention due to its role as a subnuclear compartment involved in virulence gene expression. Recent data have implicated components of the nuclear envelope in regulating gene expression in several eukaryotes. Special attention has been given to nucleoporins that compose the nuclear pore complex (NPC). However, very little is known about components of the nuclear envelope in Plasmodium parasites. Here we characterize PfSec13, an unusual nucleoporin of P. falciparum, which shows unique structural similarities suggesting that it is a fusion between Sec13 and Nup145C of yeast. Using super resolution fluorescence microscopy (3D-SIM) and in vivo imaging, we show that the dynamiclocalization of PfSec13 during parasites' intra-erythrocytic development corresponds with that of the NPCs and that these dynamics are associated with microtubules rather than with F-actin. In addition, PfSec13 does not co-localize with the heterochormatin markers HP1 and H3K9me3, suggesting euchromatic location of the NPCs. The proteins associated with PfSec13 indicate that this unusual Nup is involved in several cellular processes. Indeed, ultrastructural and chromatin immunoprecipitation analyses revealed that, in addition to the NPCs, PfSec13 is found in the nucleoplasm where it is associated with chromatin. Finally, we used peptide nucleic acids (PNA) to downregulate PfSec13 and show that it is essential for parasite proliferation in human erythrocytes. © 2013. Published by The Company of Biologists Ltd.	en_US
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT0571905
dc.relation.ispartof	Journal of Cell Science	en_US
dc.relation.isbasedon	10.1242/jcs.122119	en_US
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Erythrocytes	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Cell Nucleus	en_US
dc.subject.mesh	Chromatin	en_US
dc.subject.mesh	Microtubules	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Plasmodium falciparum	en_US
dc.subject.mesh	Malaria, Falciparum	en_US
dc.subject.mesh	Nuclear Pore Complex Proteins	en_US
dc.subject.mesh	Saccharomyces cerevisiae Proteins	en_US
dc.subject.mesh	Oligonucleotides, Antisense	en_US
dc.subject.mesh	Sequence Alignment	en_US
dc.subject.mesh	Gene Expression Regulation, Developmental	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Structural Homology, Protein	en_US
dc.subject.mesh	Protein Transport	en_US
dc.subject.mesh	Transgenes	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.title	Pfsec13 is an unusual chromatin-associated nucleoporin of plasmodium falciparum that is essential for parasite proliferation in human erythrocytes	en_US
dc.type	Journal Article
utslib.citation.volume	14	en_US
utslib.citation.volume	126	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	14	en_US
pubs.publication-status	Published	en_US
pubs.volume	126	en_US

Abstract:

In Plasmodium falciparum, the deadliest form of human malaria, the nuclear periphery has drawn much attention due to its role as a subnuclear compartment involved in virulence gene expression. Recent data have implicated components of the nuclear envelope in regulating gene expression in several eukaryotes. Special attention has been given to nucleoporins that compose the nuclear pore complex (NPC). However, very little is known about components of the nuclear envelope in Plasmodium parasites. Here we characterize PfSec13, an unusual nucleoporin of P. falciparum, which shows unique structural similarities suggesting that it is a fusion between Sec13 and Nup145C of yeast. Using super resolution fluorescence microscopy (3D-SIM) and in vivo imaging, we show that the dynamiclocalization of PfSec13 during parasites' intra-erythrocytic development corresponds with that of the NPCs and that these dynamics are associated with microtubules rather than with F-actin. In addition, PfSec13 does not co-localize with the heterochormatin markers HP1 and H3K9me3, suggesting euchromatic location of the NPCs. The proteins associated with PfSec13 indicate that this unusual Nup is involved in several cellular processes. Indeed, ultrastructural and chromatin immunoprecipitation analyses revealed that, in addition to the NPCs, PfSec13 is found in the nucleoplasm where it is associated with chromatin. Finally, we used peptide nucleic acids (PNA) to downregulate PfSec13 and show that it is essential for parasite proliferation in human erythrocytes. © 2013. Published by The Company of Biologists Ltd.

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http://hdl.handle.net/10453/26514