TXNIP 与 GLUT1 的相互作用依赖于 PI(4,5)P。
TXNIP interaction with GLUT1 depends on PI(4,5)P.
机构信息
Van Andel Institute, Grand Rapids, MI 49503, USA.
Van Andel Institute, Grand Rapids, MI 49503, USA.
出版信息
Biochim Biophys Acta Biomembr. 2021 Dec 1;1863(12):183757. doi: 10.1016/j.bbamem.2021.183757. Epub 2021 Aug 31.
Abstract
GLUT1 is a major glucose facilitator expressed ubiquitously among tissues. Upregulation of its expression plays an important role in the development of many types of cancer and metabolic diseases. Thioredoxin-interacting protein (TXNIP) is an α-arrestin that acts as an adaptor for GLUT1 in clathrin-mediated endocytosis. It regulates cellular glucose uptake in response to both intracellular and extracellular signals via its control on GLUT1-4. In order to understand the interaction between GLUT1 and TXNIP, we generated GLUT1 lipid nanodiscs and carried out isothermal titration calorimetry and single-particle electron microscopy experiments. We found that GLUT1 lipid nanodiscs and TXNIP interact in a 1:1 ratio and that this interaction requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P or PIP).
摘要
GLUT1 是一种广泛表达于组织中的主要葡萄糖转运体。其表达的上调在多种类型的癌症和代谢性疾病的发生发展中发挥着重要作用。硫氧还蛋白相互作用蛋白 (TXNIP) 是一种 α-抑制蛋白，作为网格蛋白介导的内吞作用中 GLUT1 的衔接蛋白。它通过控制 GLUT1-4 来响应细胞内外信号调节细胞葡萄糖摄取。为了了解 GLUT1 和 TXNIP 之间的相互作用，我们生成了 GLUT1 脂质纳米盘，并进行了等温滴定量热法和单颗粒电子显微镜实验。我们发现 GLUT1 脂质纳米盘与 TXNIP 以 1:1 的比例相互作用，这种相互作用需要磷脂酰肌醇 4,5-二磷酸 (PI(4,5)P 或 PIP)。
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