Dataset Information

Sub-minute phosphoregulation of cell-cycle systems during Plasmodium gamete formation revealed by a high-resolution time course

ABSTRACT: As a first step in the transmission of malaria, Plasmodium parasites ingested by a mosquito must rapidly initiate a gametogenesis process prior to sexual reproduction. The phosphorylation-based signalling mechanisms underlying the initiation of this process remain largely unmapped. We have measured a high-resolution time course of phosphorylation in P. berghei gametocytes during the first minute of gametogenesis to elucidate the scope and dynamics of the response. The data reveals rapid phosphoregulation of microtubule motor proteins and DNA replication initiation proteins within the first 18 s and of DNA replication machinery by 60 s. The data also implicate several protein kinases and phosphatases in the gametogenesis signalling pathway. Through gene knock-out experiments, we verify that the protein kinases CDPK4 and SRPK1 have distinct influences over the phosphorylation of similar downstream targets. Together, the results show that key cell-cycle systems related to both replication and mitosis undergo simultaneous, rapid phosphoregulation.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion

ORGANISM(S): Plasmodium Berghei Anka Mus Musculus (mouse)

DISEASE(S): Malaria

SUBMITTER: James Wright

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD006266 | Pride | 2017-11-29

REPOSITORIES: Pride

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Publications

Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation.

Invergo Brandon M BM Brochet Mathieu M Yu Lu L Choudhary Jyoti J Beltrao Pedro P Billker Oliver O

Cell reports 20171101 7

The transmission of malaria parasites to mosquitoes relies on the rapid induction of sexual reproduction upon their ingestion into a blood meal. Haploid female and male gametocytes become activated and emerge from their host cells, and the males enter the cell cycle to produce eight microgametes. The synchronized nature of gametogenesis allowed us to investigate phosphorylation signaling during its first minute in Plasmodium berghei via a high-resolution time course of the phosphoproteome. This ...[more]

PMID: 29141230

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Project description:Background: Mycobacterium avium subspecies paratuberculosis (MPTb) is the causative agent of Johne’s disease, an intestinal disease of ruminants with major economic consequences. MPTb bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to MPTb infection can provide valuable insights into the molecular mechanisms that underlie Johne’s disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro infection with MPTb (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection. Results: Differentially expressed genes were identified by comparing the transcriptomes of the infected MDM to the control MDM at each time point (adjusted P-value threshold ≤ 0.10). 1,050 differentially expressed unique genes were identified 2 hours post-infection, with 974 and 84 differentially expressed unique genes detected 6 hours and 24 hours post-infection, respectively. Furthermore, in the infected MDM the number of upregulated genes exceeded the number of downregulated genes at each time point, with the fold-change in expression for the upregulated genes markedly higher than that for the downregulated genes. Conclusions: Inspection and systems analysis of the differentially expressed genes revealed changes in the expression profiles of genes involved in the inflammatory response, cell signalling pathways and apoptosis. The transcriptional changes associated with cellular signalling and the inflammatory response may reflect different immuno-modulatory mechanisms that underlie host-pathogen interactions during infection. Affymetrix GeneChip® Bovine Genome Arrays were used to examine gene expression of bovine monocyte-derived macrophages (MDM) after in vitro challenge with Mycobacterium avium subspecies paratuberculosis across a time series of 2 hr, 6 hr and 24 hr post-challenge. A 0 hr control treatment was also generated and seven different age-matched female Holstein-Friesian cattle were used for each time-point/treatment combination for a total of 49 microarrays, one of which was excluded from analysis since it did not pass quality control.

Dataset Information

Sub-minute phosphoregulation of cell-cycle systems during Plasmodium gamete formation revealed by a high-resolution time course

Publications

Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation.

Similar Datasets

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