A choline-releasing glycerophosphodiesterase essential for phosphatidylcholine biosynthesis and blood stage development in the malaria parasite
Year: 2022
Type: article
Abstract: synthesizes significant amounts of phospholipids to meet the demands of replication within red blood cells. De novo phosphatidylcholine (PC) biosynthesis via the Kennedy pathway is essential, requiring choline that is primarily sourced from host serum lysophosphatidylcholine (lysoPC). LysoPC also acts as an environmental sensor to regulate parasite sexual differentiation. Despite these critical roles for host lysoPC, the enzyme(s) involved in its breakdown to free choline for PC synthesis are unknown. Here, we show that a parasite glycerophosphodiesterase (PfGDPD) is indispensable for blood stage parasite proliferation. Exogenous choline rescues growth of PfGDPD-null parasites, directly linking PfGDPD function to choline incorporation. Genetic ablation of PfGDPD reduces choline uptake from lysoPC, resulting in depletion of several PC species in the parasite, whilst purified PfGDPD releases choline from glycerophosphocholine in vitro. Our results identify PfGDPD as a choline-releasing glycerophosphodiesterase that mediates a critical step in PC biosynthesis and parasite survival.
Source: eLife
DOI: 10.7554/elife.82207
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1337751791, Role of perforin-like proteins and phospholipases in malaria parasite egress, G166206288, G1982156255, G3262181870, G3316048020, G3542850539, G366052922, Proposal for a Talos L120C G2 Transmission Electron Microscope, G3800792004, G5444891929, G5738870174, G6371360578, G6409301863, Funktionelle Charakterisierung der Phospholipasen im Malariaerreger Plasmodium falciparum, G6624823929, G6656207352, G818327338, G8577269960
OpenAlex ID: W4313237556