title: PfSec13 is an unusual chromatin-associated nucleoporin of Plasmodium falciparum that is essential for parasite proliferation in human erythrocytes.
abstract: In Plasmodium falciparum, the deadliest form of human malaria, the nuclear periphery has drawn much attention due to its role as a sub-nuclear 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 dynamic localization 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Institute for Medical Research Israel-Canada, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Dahan-Pasternak
authors.forename: Abed
authors.initials: A
authors.lastname: Nasereddin
authors.forename: Netanel
authors.initials: N
authors.lastname: Kolevzon
authors.forename: Michael
authors.initials: M
authors.lastname: Pe'er
authors.forename: Wilson
authors.initials: W
authors.lastname: Wong
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Lynne
authors.initials: L
authors.lastname: Turnbull
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Whitchurch
authors.forename: Michael
authors.initials: M
authors.lastname: Elbaum
authors.forename: Tim W
authors.initials: TW
authors.lastname: Gilberger
authors.forename: Eylon
authors.initials: E
authors.lastname: Yavin
authors.forename: Jake
authors.initials: J
authors.lastname: Baum
authors.forename: Ron
authors.initials: R
authors.lastname: Dzikowski
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology* / Q000503:physiopathology; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010963:Plasmodium falciparum / Q000378:metabolism / Q000472:pathogenicity*; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D019076:Transgenes / Q000235:genetics
chemical_list: D002843:Chromatin; C088627:NUP145 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D016376:Oligonucleotides, Antisense; C079620:SEC13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: Chromatin; Gene expression; Malaria; Nuclear pore complex; Nup; Plasmodium falciparum