Proteomics

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Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes


ABSTRACT: Asexual proliferation of the Plasmodium parasites that cause malaria follow a developmental program that alternates non-canonical intraerythrocytic replication with dissemination to new host cells. We carried out a functional analysis of the Plasmodium falciparum homolog of Protein Phosphatase 1 (PfPP1), a universally conserved cell cycle factor in eukaryotes, to investigate regulation of parasite proliferation. PfPP1 is indeed required for efficient replication, but is absolutely essential for egress of parasites from host red blood cells. By phosphoproteomic and chemical-genetic analysis, we isolate two functional targets of PfPP1 for egress: a HECT E3 protein-ubiquitin ligase; and GCalpha, a fusion protein composed of a guanylyl cyclase and a phospholipid transporter domain. We hypothesize that PfPP1 regulates lipid sensing by GCalpha and demonstrate that phosphatidylcholine stimulates PfPP1-dependent egress. PfPP1 acts as a key regulator that integrates multiple cell-intrinsic pathways with external signals to direct parasite egress from host cells.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Plasmodium Falciparum Dd2

SUBMITTER: Joao Paulo  

LAB HEAD: Joao A. Paulo

PROVIDER: PXD018718 | Pride | 2020-08-11

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
203727_m07560_PlasPro.mzIdentML Mzid
203728_m07561_PlasPro.mzIdentML Mzid
203729_m07562_PlasPro.mzIdentML Mzid
203730_m07563_PlasPro.mzIdentML Mzid
203731_m07564_PlasPro.mzIdentML Mzid
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Asexual proliferation of the Plasmodium parasites that cause malaria follows a developmental program that alternates non-canonical intraerythrocytic replication with dissemination to new host cells. We carried out a functional analysis of the Plasmodium falciparum homolog of Protein Phosphatase 1 (PfPP1), a universally conserved cell cycle factor in eukaryotes, to investigate regulation of parasite proliferation. PfPP1 is indeed required for efficient replication, but is absolutely essential for  ...[more]

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