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张力蛋白-2 相互作用组学揭示了与 GAPDH 的相互作用以及在糖酵解中的磷酸化介导的调节作用。

Tensin-2 interactomics reveals interaction with GAPDH and a phosphorylation-mediated regulatory role in glycolysis.

机构信息

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Fimlab Laboratories, Tampere, Finland.

出版信息

Sci Rep. 2024 Aug 27;14(1):19862. doi: 10.1038/s41598-024-65787-7.

DOI:10.1038/s41598-024-65787-7
PMID:39191795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11350193/
Abstract

Integrin adaptor proteins, like tensin-2, are crucial for cell adhesion and signaling. However, the function of tensin-2 beyond localizing to focal adhesions remain poorly understood. We utilized proximity-dependent biotinylation and Strep-tag affinity proteomics to identify interaction partners of tensin-2 in Flp-In 293 T-REx cells. Interactomics linked tensin-2 to known focal adhesion proteins and the dystrophin glycoprotein complex, while also uncovering novel interaction with the glycolytic enzyme GAPDH. We demonstrated that Y483-phosphorylation of tensin-2 regulates the glycolytic rate in Flp-In 293 T-REx and MEF cells and found that pY483 tensin-2 is enriched in adhesions in MEF cells. Our study unveils novel interaction partners for tensin-2 and further solidifies its speculated role in cell energy metabolism. These findings shed fresh insight on the functions of tensin-2, highlighting its potential as a therapeutic target for diseases associated with impaired cell adhesion and metabolism.

摘要

整合素衔接蛋白，如张力蛋白-2，对于细胞黏附和信号转导至关重要。然而，张力蛋白-2在黏附斑以外的功能仍知之甚少。我们利用邻近依赖性生物素化和链霉亲和素亲和蛋白质组学，在 Flp-In 293 T-REx 细胞中鉴定张力蛋白-2的相互作用伙伴。相互作用组学将张力蛋白-2与已知的黏附斑蛋白和肌营养不良糖蛋白复合物联系起来，同时还揭示了与糖酵解酶 GAPDH 的新相互作用。我们证明了张力蛋白-2的 Y483 磷酸化调节 Flp-In 293 T-REx 和 MEF 细胞的糖酵解速率，并发现 pY483 张力蛋白-2在 MEF 细胞的黏附斑中富集。我们的研究揭示了张力蛋白-2的新的相互作用伙伴，并进一步证实了其在细胞能量代谢中的推测作用。这些发现为张力蛋白-2的功能提供了新的见解，突出了其作为与细胞黏附受损和代谢紊乱相关疾病的治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a00f/11350193/e47bfeadce69/41598_2024_65787_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a00f/11350193/e47bfeadce69/41598_2024_65787_Fig7_HTML.jpg
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本文引用的文献

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DeepLoc 2.0: multi-label subcellular localization prediction using protein language models.DeepLoc 2.0：使用蛋白质语言模型进行多标签亚细胞定位预测。
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The GAS6-AXL signaling pathway triggers actin remodeling that drives membrane ruffling, macropinocytosis, and cancer-cell invasion.GAS6-AXL 信号通路触发肌动蛋白重塑，从而驱动细胞膜皱襞形成、巨胞饮作用和癌细胞侵袭。
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Tensins - emerging insights into their domain functions, biological roles and disease relevance.张力蛋白 - 对其结构域功能、生物学作用和疾病相关性的新认识。
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ABCA12 regulates insulin secretion from β-cells.ABCA12 调节β细胞胰岛素分泌。
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