دورية أكاديمية
Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.
| العنوان: | Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness. |
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| المؤلفون: | Koutsogiannis Z; Department of Biosciences, Durham University, Durham, UK., Mina JG; Department of Biosciences, Durham University, Durham, UK., Albus CA; Department of Biosciences, Durham University, Durham, UK., Kol MA; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany., Holthuis JCM; Molecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany., Pohl E; Department of Biosciences, Durham University, Durham, UK.; Department of Chemistry, Durham University, Durham, UK., Denny PW; Department of Biosciences, Durham University, Durham, UK. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2023 Nov; Vol. 37 (11), pp. e23229. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Toxoplasma*/genetics , Parasites*, Humans ; Animals ; Gene Duplication ; Phylogeny ; Sphingolipids ; Ceramides/genetics ; Protozoan Proteins/genetics |
| مستخلص: | 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 TgCerS1 and TgCerS2. Interestingly, we observed that while TgCerS1 was a fully functional orthologue of the yeast ceramide synthase (Lag1p) capable of catalyzing the conversion of sphinganine to ceramide, in contrast TgCerS2 was catalytically inactive. Furthermore, genomic deletion of TgCerS1 using CRISPR/Cas-9 led to viable but slow-growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of TgCerS2 was only accessible utilizing the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this "pseudo" ceramide synthase, TgCerS2, has a considerably greater role in parasite fitness than its catalytically active orthologue (TgCerS1). 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. (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.) |
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| معلومات مُعتمدة: | MR/P027989/1 United Kingdom MRC_ Medical Research Council; BB/T003987/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; BB/M024156/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
| المشرفين على المادة: | EC 1.3.1.- (dihydroceramide desaturase) 0 (Sphingolipids) 0 (Ceramides) 0 (Protozoan Proteins) |
| تواريخ الأحداث: | Date Created: 20231005 Date Completed: 20231027 Latest Revision: 20240320 |
| رمز التحديث: | 20240320 |
| مُعرف محوري في PubMed: | PMC10946778 |
| DOI: | 10.1096/fj.202201603RRR |
| PMID: | 37795915 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.202201603RRR |