DEFINING THE MOLECULAR COMPONENTS OF GLUT4 TRANSLOCATION

定义 GLUT4 易位的分子成分

• 批准号: 2623978
• 负责人: Bentley Cheatham
• 金额: $ 14.59万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-26 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2623978
• 关键词: adipocytes; binding proteins; biological signal transduction; cell line; chimeric proteins; exocytosis; glucose metabolism; glucose transport; glucose transporter; guanine nucleotide binding protein; hormone regulation /control mechanism; immunoprecipitation; insulin; intermolecular interaction; intracellular transport; membrane fusion; membrane proteins; molecular cloning; mutant; protein purification; synthetic peptide; vesicle /vacuole; western blottings

In adipose tissue and skeletal muscle insulin induces the translocation o f GLUT4-containing vesicles to the ell surface resulting in an increase in glucose uptake. The mechanism of GLUT4 translocation is poorly understood. Recently several proteins involved in regulated exocytosis in neural and neuroendocrine tissues have been shown to be expressed in insulin-sensitive tissues. These proteins are components of the SNARE complex. In addition, members of the RAB family of small GTP-binding proteins that are involved in regulated endocytosis/exocytosis are also present in adipocytes and skeletal muscle. While these proteins have been implicated in insulin-regulated GLUT4 translocation no functional role has been determined. However, we have recently established that SNARE- complex proteins and specific members of the Rab family are necessary components in the GLUT4 translocation machinery. We have also identified a potentially novel protein that interacts with Rabs in adipocytes in an insulin-regulated manner. It is the purpose of this proposal to extend our preliminary observations to include a more detailed biochemical and cell biological analysis of these molecules. These studies will include experiments designed to investigate the specificity of protein-protein interactions between the SNARE proteins and their regulation by insulin, identification of other novel Rab-interacting proteins and pursuit of their molecular cloning. Data from these studies will allow us to define a more contemporary model of insulin-regulated glucose uptake.

在脂肪组织和骨骼肌胰岛素中，诱导易位 含Glut4的囊泡到ELL表面，导致 葡萄糖摄取的增加。 GLUT4易位的机制 理解很差。 最近几种涉及调节的蛋白质 神经和神经内分泌组织中的胞吐作用已显示为 在胰岛素敏感组织中表达。 这些蛋白质是 军鼓复合物的组成部分。 此外， 涉及的小型GTP结合蛋白的Rab家族 脂肪细胞中也存在调节的内吞和胞吞作用 骨骼肌。 尽管这些蛋白质与 胰岛素调节的GLUT4易位没有功能的作用 决定。 但是，我们最近确定了这一点 - 复杂的蛋白质和Rab家族的特定成员是 GLUT4易位机械中的必要组件。我们 还确定了一种潜在的新型蛋白质，与 脂肪细胞中的兔子以胰岛素调节的方式。 这是目的 该提议将我们的初步观察扩展到包括 对这些的更详细的生化和细胞生物学分析 分子。 这些研究将包括设计为 研究蛋白质 - 蛋白质相互作用的特异性 网罗蛋白质及其通过胰岛素调节，鉴定 其他新型的Rab Itteracting蛋白和追求分子的追求 克隆。 这些研究的数据将使我们能够定义更多 胰岛素调节的葡萄糖摄取的当代模型。