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Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE189197 | GEO | 2021/11/21

REPOSITORIES: GEO

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The transcriptional regulator HDP1 controls expansion of the inner membrane complex during early sexual differentiation of malaria parasites.

Project description:Transmission of Plasmodium falciparum and other malaria parasites requires their differentiation from asexual blood stages into gametocytes, the non-replicative sexual stage necessary to infect the mosquito vector. This transition involves changes in gene expression and chromatin reorganization that result in the activation and silencing of stage-specific genes. However, the genomes of malaria parasites have been noted for their limited number of transcriptional and chromatin regulators, and the molecular mediators of these changes remain largely unknown. We recently identified homeodomain protein 1 (HDP1) as a DNA-binding protein, first expressed in gametocytes, that enhances the expression of key genes critical for early sexual differentiation. The discovery of HDP1 marks a new class of transcriptional regulator in malaria parasites outside of the better-characterized ApiAP2 family. Here, using molecular biology, biochemistry and microscopy techniques, we show that HDP1 is essential for gametocyte maturation, facilitating the necessary upregulation of inner membrane complex components during early gametocytogenesis that gives P. falciparum gametocytes their characteristic shape.

| S-EPMC8852293 | biostudies-literature

Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [RNA-Seq]

Project description:In this study, we identify HDP1, a previously uncharacterized DNA-binding protein first expressed during early sexual differentiation. The development of HDP1-deficient gametocytes arrests at the Stage I to Stage II transition and ends in loss of viability. Analysis of gene expression and HDP1-binding shows that this protein functions as a positive transcriptional regulator of genes essential for gametocyte development, including genes that are critical for the expansion of the inner membrane complex (IMC) that gives P. falciparum gametocytes their characteristic shape.

2021-11-21 | GSE189196 | GEO

Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [ChIP-Seq]

2021-11-21 | GSE189151 | GEO

Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites

Project description:Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites

| PRJNA781928 | ENA

Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [RNA-Seq]

Project description:Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [RNA-Seq]

| PRJNA781941 | ENA

Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [ChIP-Seq]

Project description:Transcriptional regulator HDP1 regulates expansion of the inner membrane complex during early sexual differentiation of malaria parasites [ChIP-Seq]

| PRJNA781649 | ENA

Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development.

Project description:Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1. Genetic disruption of PhIL1 or PIP1 ablates elongation and prevents formation of transmission-ready mature gametocytes. The maturation defect is accompanied by failure to form an enveloping IMC and a marked swelling of the digestive vacuole, suggesting PhIL1 and PIP1 are required for correct membrane trafficking. Using immunoprecipitation and mass spectrometry we reveal that PhIL1 interacts with known and new components of the gametocyte IMC.

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An exon DNA element modulates heterochromatin spreading in the master regulator for sexual commitment in malaria parasites

Project description:Heterochromatin is essential in all eukaryotic systems to maintain genome integrity, long-term gene repression and to help chromosome segregation during mitosis. However, heterochromatin regions must be restricted by boundary elements to avoid its spreading over actively transcribed loci. In Plasmodium falciparum, facultative heterochromatin is important to regulate parasite virulence, antigenic variation and transmission, but the underlying molecular mechanisms that regulate repressive regions remain unknown. To investigate this topic, we chose the ap2-g gene, that forms a strictly delimited heterochromatin island of 10 kb with no adjacent repressive chromatin. Using electrophoretic motility shift assay (EMSA) we identified an ap2-g exon element at the 3? end that shifts in the presence of nuclear extracts. Upon replacement of this region by a gfp gene, we observed a shift in the heterochromatin boundary, resulting in HP1 to spread over ~2 additional kb downstream. We used this DNA element to affinity purify candidate proteins followed by liquid-chromatography tandem mass-spectrometry (LC-MS/MS). The identified complexes are enriched in RNA-binding proteins, pointing to a potential role of RNA in the regulation of the ap2-g heterochromatin 3? boundary. Our results provide insight into the unexplored topic of heterochromatin boundary biology in P. falciparum and identifies a DNA element in the master regulator of sexual commitment that modulates heterochromatin spreading.

2020-02-18 | GSE145378 | GEO

Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite.

Project description:Malaria is caused by infection of the erythrocytes by the parasites Plasmodium. Inside the erythrocytes, the parasites multiply via schizogony, an unconventional cell division mode. The inner membrane complex (IMC), an organelle located beneath the parasite plasma membrane, serving as the platform for protein anchorage, is essential for schizogony. So far, the complete repertoire of IMC proteins and their localization determinants remain unclear. Here we used biotin ligase (TurboID)-based proximity labeling to compile the proteome of the schizont IMC of the rodent malaria parasite Plasmodium yoelii. In total, 300 TurboID-interacting proteins were identified. 18 of 21 selected candidates were confirmed to localize in the IMC, indicating good reliability. In light of the existing palmitome of Plasmodium falciparum, 83 proteins of the P. yoelii IMC proteome are potentially palmitoylated. We further identified DHHC2 as the major resident palmitoyl-acyl-transferase of the IMC. Depletion of DHHC2 led to defective schizont segmentation and growth arrest both in vitro and in vivo. DHHC2 was found to palmitoylate two critical IMC proteins CDPK1 and GAP45 for their IMC localization. In summary, this study reports an inventory of new IMC proteins and demonstrates a central role of DHHC2 in governing the IMC localization of proteins during the schizont development.

| S-EPMC9293000 | biostudies-literature

Regulation of sexual differentiation is linked to invasion in malaria parasites

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-02-08 | GSE125566 | GEO