In:
The FASEB Journal, Wiley, Vol. 37, No. 11 ( 2023-11)
Abstract:
Toxoplasma gondii is an obligate, intracellular apicomplexan protozoan parasite of both humans and animals that can cause fetal damage and abortion and severe disease in the immunosuppressed. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localization and analyses of the Toxoplasma ceramide synthases Tg CerS1 and Tg CerS2. Interestingly, we observed that while Tg CerS1 was a fully functional orthologue of the yeast ceramide synthase (Lag1p) capable of catalyzing the conversion of sphinganine to ceramide, in contrast Tg CerS2 was catalytically inactive. Furthermore, genomic deletion of Tg CerS1 using CRISPR/Cas‐9 led to viable but slow‐growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of Tg CerS2 was only accessible utilizing the rapamycin‐inducible Cre recombinase system. Surprisingly, the results demonstrated that this “pseudo” ceramide synthase, Tg CerS2, has a considerably greater role in parasite fitness than its catalytically active orthologue ( Tg CerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa may have arisen through gene duplication. However, in the Apicomplexa the duplicated copy is hypothesized to have subsequently evolved into a non‐functional “pseudo” ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites.
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fj.202201603RRR
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
1468876-1
SSG:
12
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