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PILS-Nir1是一种灵敏的磷脂酸生物传感器，可揭示脂质产生的机制。

PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production.

作者信息

Weckerly Claire C, Rahn Taylor A, Ehrlich Max, Wills Rachel C, Pemberton Joshua G, Airola Michael V, Hammond Gerald R V

机构信息

Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.

出版信息

J Cell Biol. 2025 Nov 3;224(11). doi: 10.1083/jcb.202405174. Epub 2025 Sep 9.

DOI:10.1083/jcb.202405174
PMID:40923975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12419160/
Abstract

Phosphatidic acid (PA) regulates lipid homeostasis and vesicular trafficking, yet high-affinity tools to study PA in live cells are lacking. We identified the lipin-like sequence of Nir1 (PILS-Nir1) as a candidate PA biosensor based on structural analysis of Nir1's LNS2 domain. Using liposome-binding assays and pharmacological and genetic manipulations in HEK293A cells expressing fluorescent PILS-Nir1, we found that while PILS-Nir1 binds PA and PIP2in vitro, only PA is necessary and sufficient for membrane localization in cells. PILS-Nir1 displayed greater sensitivity to organelle-generated PA than Spo20-based probes, enabling visualization of modest PA production by PLD downstream of muscarinic receptors-previously undetectable with existing biosensors. Thus, PILS-Nir1 provides a versatile, sensitive tool for real-time PA dynamics in live cells.

摘要

磷脂酸（PA）调节脂质稳态和囊泡运输，但缺乏用于在活细胞中研究PA的高亲和力工具。基于Nir1的LNS2结构域的结构分析，我们将Nir1的类脂素序列（PILS-Nir1）鉴定为候选PA生物传感器。通过在表达荧光PILS-Nir1的HEK293A细胞中进行脂质体结合试验以及药理学和遗传学操作，我们发现虽然PILS-Nir1在体外结合PA和PIP2，但只有PA对于细胞中的膜定位是必需且足够的。与基于Spo20的探针相比，PILS-Nir1对细胞器产生的PA表现出更高的敏感性，能够可视化毒蕈碱受体下游PLD产生的适度PA——这是现有生物传感器以前无法检测到的。因此，PILS-Nir1为活细胞中实时PA动态提供了一种通用、灵敏的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/c3173423d71c/jcb_202405174_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/015a6e3f2780/jcb_202405174_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/619a2e6dd706/jcb_202405174_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/4e00def7df5c/jcb_202405174_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/44a8797182ea/jcb_202405174_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/20d16c86a0e2/jcb_202405174_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/43339fd4f1ed/jcb_202405174_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/9e60ec750835/jcb_202405174_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/7a74843138e4/jcb_202405174_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/c3173423d71c/jcb_202405174_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/015a6e3f2780/jcb_202405174_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/619a2e6dd706/jcb_202405174_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/4e00def7df5c/jcb_202405174_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/44a8797182ea/jcb_202405174_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/20d16c86a0e2/jcb_202405174_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/43339fd4f1ed/jcb_202405174_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/9e60ec750835/jcb_202405174_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/7a74843138e4/jcb_202405174_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fbe/12419160/c3173423d71c/jcb_202405174_fig7.jpg

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