How does EFR3 control insulin-stimulated plasma membrane dispersal of GLUT4?

EFR3 如何控制胰岛素刺激的 GLUT4 质膜扩散？

• 批准号: BB/X005178/1
• 负责人: Gwyn William Gould
• 金额: $ 61.4万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX005178%2F1
• 关键词: How; does; EFR3; control; insulin

All cells are surrounded by a structure called the plasma membrane. This provides protection for a cell and helps keep the environment inside the cell stable. The plasma membrane has several functions, including regulating what gets in and out of the cell, and helping the cell sense and respond to external events.Nutrients like sugars are transported across the plasma membrane by specialised proteins called 'transporters'. Understanding how these nutrient transporters are controlled is important, as depending on the conditions a cell may need to increase or decrease the rate of entry of a particular nutrient, perhaps in response to a specific cue.Our group studies how sugar (glucose) transport is regulated, and in particular how this is regulated by a hormone called insulin. Insulin plays an important role in helping keep blood sugar levels constant by controlling the rate by which sugar crosses the plasma membrane of fat and muscle. Defective glucose transport is associated with diseases such as diabetes and also some neurological disorders, hence understanding how transporter proteins are regulated may have considerable impact.Our group has uncovered a new way in which membrane transporters are controlled. We have found that insulin acts to 'disperse' glucose transporters. In the absence of insulin transporters are clustered together (rather like sheep in a pen). Insulin acts to open the gates to the pen and allow the transporters to rapidly move around in the plasma membrane so that they can function effectively and allow glucose transport.We have been able to gain some clues to how a cell does this, and here we seek to further understand how this dispersal is controlled, to ask whether this is specific for sugar transporters or if it is displayed by other nutrient transporters (or happens to all plasma membrane proteins), and we will look to understand how hormones like insulin induce a change in clustering.Our work will, we believe, be of wide interest to colleagues who study cell membrane function from both a basic biology and a translational standpoint. To address these questions, we have created a team of biologists, physicists, and electronics experts to bring their skills to bear on a common problem of fundamental importance.

所有的细胞都被一种叫做质膜的结构所包围。这为细胞提供保护，并有助于保持细胞内环境的稳定。质膜有几种功能，包括调节进出细胞的物质，帮助细胞感知和应对外部事件。糖等营养物质通过称为“转运体”的特殊蛋白质在质膜上运输。了解这些营养转运蛋白是如何被控制的很重要，因为根据细胞可能需要增加或减少特定营养物质进入的速度的条件，可能是为了对特定的信号做出反应。我们的团队研究了糖(葡萄糖)运输是如何被调节的，特别是它是如何被称为胰岛素的激素调节的。胰岛素通过控制糖穿过脂肪和肌肉质膜的速度，在帮助保持血糖水平稳定方面发挥着重要作用。葡萄糖转运缺陷与糖尿病等疾病和一些神经疾病有关，因此了解转运蛋白是如何调控的可能会产生相当大的影响。我们的团队发现了一种控制膜转运蛋白的新方法。我们发现，胰岛素起到“分散”葡萄糖转运蛋白的作用。在没有胰岛素转运体的情况下，胰岛素转运体聚集在一起(有点像羊圈里的羊)。胰岛素的作用是打开转运蛋白的大门，让转运蛋白在质膜中快速移动，从而有效地发挥作用，并允许葡萄糖的运输。我们已经能够获得一些细胞如何做到这一点的线索，在这里我们试图进一步了解这种扩散是如何被控制的，询问这是糖转运蛋白所特有的，还是其他营养转运蛋白(或所有质膜蛋白都存在)所显示的，我们将寻求了解像胰岛素这样的激素是如何诱导聚集的变化的。我们相信，我们的工作将会对从基础生物学和翻译角度研究细胞膜功能的同事产生广泛的兴趣。为了解决这些问题，我们组建了一个由生物学家、物理学家和电子学专家组成的团队，将他们的技能运用到一个具有根本重要性的共同问题上。