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

Nature Communications
A. S. PaulManoj T Duraisingh

Abstract

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 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 GCα, a fusion protein composed of a guanylyl cyclase and a phospholipid transporter domain. We hypothesize that PfPP1 regulates lipid sensing by GCα and find 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.

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Citations

Nov 26, 2020·Molecular Microbiology·Manish KumarManoj T Duraisingh
Oct 11, 2020·Trends in Parasitology·Jamal KhalifeChristine Pierrot
Mar 10, 2021·Journal of Cell Science·Michele S Y Tan, Michael J Blackman
Apr 30, 2021·Frontiers in Cellular and Infection Microbiology·Marc-Jan GubbelsKlemens Engelberg
Jul 27, 2021·Parasitology Research·Jenny Nancy Gómez-SandovalM Magdalena Aguirre-García
Aug 31, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Margarida Ressurreição, Christiaan van Ooij

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Methods Mentioned

BETA
transgenic
flow-cytometry
light microscopy
electron microscopy
ubiquitination
PCR
affinity purification
transmission electron microscopy
ELISA
acetylation

Software Mentioned

Prism
Fiji 82
SEQUEST
GraphPad
Zen

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