Abstract
The nuclear pore complex (NPC) is a large macromolecular assembly of around 30 different proteins, so-called nucleoporins (Nups). Embedded in the nuclear envelope the NPC mediates bi-directional exchange between the cytoplasm and the nucleus and plays a role in transcriptional regulation that is poorly understood. NPCs display modular arrangements with an overall structure that is generally conserved among many eukaryotic phyla. However, Nups of yeast or human origin show little primary sequence conservation with those from early-branching protozoans leaving those of the malaria parasite unrecognized. Here we have combined bioinformatic and genetic methods to identify and spatially characterize Nup components in the rodent infecting parasite Plasmodium berghei and identified orthologs from the human malaria parasite P. falciparum, as well as the related apicomplexan parasite Toxoplasma gondii. For the first time we show the localization of selected Nups throughout the P. berghei life cycle. Largely restricted to apicomplexans we identify an extended C-terminal poly-proline extension in SEC13 that is essential for parasite survival and provide high-resolution images of Plasmodium NPCs obtained by cryo electron tomography. Our data provide the basis for full characterization of NPCs in malaria parasites, early branching unicellular eukaryotes with significant impact on human health.
Highlights
The nuclear envelope of eukaryotes constitutes a barrier between the nucleoplasm and the cytoplasm
Similar to the mRNA export machinery in P. falciparum[30] we find that Plasmodium nuclear pore complex (NPC) components share little sequence conservation with those from other eukaryotes
We provide a comparison of T. gondii with P. berghei Nups at all other relevant sections of this manuscript
Summary
The nuclear envelope of eukaryotes constitutes a barrier between the nucleoplasm (containing the genome) and the cytoplasm. The identification of NPC components and their study in the malaria parasite have been hampered by the small size of the parasite and the poor sequence homology between Nups from key eukaryotic model organisms with those from Plasmodium. This divergence is highlighted in a 2010 genomic study[24]. A fourth protein PF3D7_0905100 with a molecular weight of 235 kDa is annotated as Nup[100] in the Plasmodium genome repository www.plasmodb.org Three of those proteins are conserved in the rodent malaria model parasite P. berghei, but Nup[116] lacks a syntenic ortholog in P. berghei. The various Plasmodium genomes contain more than 5000 genes with more than 30% still annotated as hypothetical proteins and lacking clear homologs outside the genus
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