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表面张力驱动的人 perilipins 在脂滴上的分类。

Surface tension-driven sorting of human perilipins on lipid droplets.

机构信息

Université Côte d'Azur, CNRS and Inserm, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 , Sophia Antipolis, France.

Centre de Recherche en Biologie Cellulaire de Montpellier-CRBM, Université de Montpellier, CNRS, UMR 5237 , Montpellier, France.

出版信息

J Cell Biol. 2024 Dec 2;223(12). doi: 10.1083/jcb.202403064. Epub 2024 Sep 19.

DOI:10.1083/jcb.202403064
PMID:39297796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11413419/
Abstract

Perilipins (PLINs), the most abundant proteins on lipid droplets (LDs), display similar domain organization including amphipathic helices (AH). However, the five human PLINs bind different LDs, suggesting different modes of interaction. We established a minimal system whereby artificial LDs covered with defined polar lipids were transiently deformed to promote surface tension. Binding of purified PLIN3 and PLIN4 AH was strongly facilitated by tension but was poorly sensitive to phospholipid composition and to the presence of diacylglycerol. Accordingly, LD coverage by PLIN3 increased as phospholipid coverage decreased. In contrast, PLIN1 bound readily to LDs fully covered by phospholipids; PLIN2 showed an intermediate behavior between PLIN1 and PLIN3. In human adipocytes, PLIN3/4 were found in a soluble pool and relocated to LDs upon stimulation of fast triglyceride synthesis, whereas PLIN1 and PLIN2 localized to pre-existing LDs, consistent with the large difference in LD avidity observed in vitro. We conclude that the PLIN repertoire is adapted to handling LDs with different surface properties.

摘要

脂滴(LDs)上含量最丰富的蛋白是 perilipins(PLINs),它们具有相似的结构域组织,包括两亲性螺旋(AH)。然而,五种人类 PLIN 结合不同的 LDs,表明存在不同的相互作用模式。我们建立了一个最小的系统,其中覆盖有特定极性脂质的人工 LDs 会暂时变形以促进表面张力。纯化的 PLIN3 和 PLIN4 AH 的结合强烈地受到张力的促进,但对磷脂组成和二酰基甘油的存在不敏感。因此,随着磷脂覆盖率的降低,PLIN3 对 LD 的覆盖增加。相比之下,PLIN1 很容易与完全被磷脂覆盖的 LDs 结合;PLIN2 表现出介于 PLIN1 和 PLIN3 之间的中间行为。在人类脂肪细胞中,PLIN3/4 存在于可溶池中,在快速甘油三酯合成刺激下重新定位到 LDs,而 PLIN1 和 PLIN2 定位于预先存在的 LDs 上,这与体外观察到的 LD 亲和力的巨大差异一致。我们得出结论,PLIN 库适应于处理具有不同表面性质的 LDs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/9daebef99e12/JCB_202403064_FigS5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/9daebef99e12/JCB_202403064_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/dea7013f04fd/JCB_202403064_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/638270719a86/JCB_202403064_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/7b5af9b3ce31/JCB_202403064_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/382ad051031d/JCB_202403064_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/04dee1b63423/JCB_202403064_Fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/20026e89f1a0/JCB_202403064_FigS4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/c931ad5d73d3/JCB_202403064_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12da/11413419/f4b97ba95ea3/JCB_202403064_Fig7.jpg
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