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复杂鞘脂谱分析及一种肌醇磷酸神经酰胺合酶的鉴定。 (原文中“in.”后面内容缺失,翻译根据现有内容尽量完整呈现)

Complex sphingolipid profiling and identification of an inositol-phosphorylceramide synthase in .

作者信息

Listian Stevanus A, Mazur Anna-Carina, Kol Matthijs, Ufelmann Edwin, Eising Sebastian, Fröhlich Florian, Walter Stefan, Holthuis Joost C M, Barisch Caroline

机构信息

Division of Molecular Infection Biology, Department of Biology/Chemistry, University of Osnabrück, Osnabrück, Germany.

Centre for Structural Systems Biology, Hamburg, Germany.

出版信息

iScience. 2024 Jul 30;27(9):110609. doi: 10.1016/j.isci.2024.110609. eCollection 2024 Sep 20.

DOI:10.1016/j.isci.2024.110609
PMID:39286488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11402645/
Abstract

is a professional phagocyte frequently used to study cellular processes underlying the recognition, engulfment, and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control membrane properties, participate in signal transmission, and serve as adhesion molecules in recognition processes relevant to immunity and infection. By combining lipidomics with a bioinformatics-based cloning strategy, we show here that produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones. Cell-free expression of candidate inositol-phosphorylceramide (IPC) synthases from enabled identification of an enzyme that selectively catalyzes the transfer of phosphoinositol from phosphatidylinositol onto ceramide. The IPC synthase, IPCS1, shares multiple sequence motifs with yeast IPC and human sphingomyelin synthases and localizes to the Golgi apparatus as well as the contractile vacuole of . These findings open up important opportunities for exploring a role of sphingolipids in phagocytosis and infection across major evolutionary boundaries.

摘要

是一种专业吞噬细胞,常用于研究微生物病原体识别、吞噬和感染过程背后的细胞过程。鞘脂是质膜的丰富成分,可结合胆固醇、控制膜特性、参与信号传递,并在与免疫和感染相关的识别过程中充当粘附分子。通过将脂质组学与基于生物信息学的克隆策略相结合,我们在此表明,产生主要以植物神经酰胺为骨架的含磷酸肌醇鞘脂。来自的候选肌醇磷酸神经酰胺(IPC)合酶的无细胞表达能够鉴定出一种酶,该酶选择性地催化磷酸肌醇从磷脂酰肌醇转移到神经酰胺上。IPC合酶IPCS1与酵母IPC和人鞘磷脂合酶具有多个序列基序,并定位于的高尔基体以及收缩泡。这些发现为探索鞘脂在跨越主要进化界限的吞噬作用和感染中的作用提供了重要机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/be19e116b6fb/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/0896ab1cb993/fx1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/dd8077a30b58/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/8fde52f96119/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/3805b1311245/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/1ddf04ff4f16/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/2bcfda763efe/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/be19e116b6fb/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/0896ab1cb993/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/3a9d5183224c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/dd8077a30b58/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/8fde52f96119/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/3805b1311245/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/bf042ab94646/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/1ddf04ff4f16/gr6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c39/11402645/be19e116b6fb/gr8.jpg

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Pathogenic variants of sphingomyelin synthase SMS2 disrupt lipid landscapes in the secretory pathway.鞘磷脂合成酶 SMS2 的致病性变异破坏分泌途径中的脂质景观。
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