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。这为细胞提供了保护，并有助于保持细胞内的环境稳定。质膜具有多种功能，包括调节细胞内外的物质，帮助细胞感知和响应外部事件。糖等营养物质通过称为“转运蛋白”的特殊蛋白质跨质膜转运。了解这些营养转运蛋白是如何被控制的是很重要的，因为根据细胞可能需要的条件来增加或减少特定营养物质的进入速率，也许是为了响应特定的提示。我们的小组研究了糖（葡萄糖）转运是如何被调节的，特别是胰岛素是如何被调节的。胰岛素通过控制糖穿过脂肪和肌肉的质膜的速率，在帮助保持血糖水平恒定方面起着重要作用。葡萄糖转运缺陷与糖尿病等疾病以及一些神经系统疾病有关，因此了解转运蛋白是如何调节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。我们已经发现胰岛素的作用是“分散”葡萄糖转运蛋白。在缺乏胰岛素的情况下，转运蛋白聚集在一起（就像羊圈里的羊一样）。胰岛素的作用是打开笔的大门，使转运蛋白在质膜中快速移动，以便它们能够有效地发挥作用并允许葡萄糖转运。我们已经能够获得一些关于细胞如何做到这一点的线索，在这里我们寻求进一步了解这种分散是如何控制的，询问这是否是糖转运蛋白特有的，或者其他营养转运蛋白是否也有这种情况（或发生在所有质膜蛋白），我们将着眼于了解激素如胰岛素如何诱导聚集的变化。我们的工作将，我们相信，从基础生物学和翻译的角度研究细胞膜功能的同事们都很感兴趣。为了解决这些问题，我们成立了一个由生物学家、物理学家和电子专家组成的团队，利用他们的技能来解决一个具有根本重要性的共同问题。