Regulation of Glut 1 Function

Glut 1 功能的调节

• 批准号: 6685004
• 负责人: FARAMARZ ISMAIL-BEIGI
• 金额: $ 32.51万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6685004
• 关键词: binding proteins; cell membrane; electron microscopy; fatty acylation; genetically modified animals; glucose transporter; immunoprecipitation; laboratory mouse; membrane proteins; oxidative phosphorylation; palmitates; posttranslational modifications; protein binding; protein kinase; protein localization; protein protein interaction; protein structure function; protein transport; tissue /cell culture; binding proteins; cell membrane; electron microscopy; fatty acylation; genetically modified animals; glucose transporter; immunoprecipitation; laboratory mouse; membrane proteins; oxidative phosphorylation; palmitates; posttranslational modifications; protein binding; protein kinase; protein localization; protein protein interaction; protein structure function; protein transport; tissue /cell culture

DESCRIPTION (provided by applicant): Glut1 glucose transporter is an integral plasma membrane protein that is expressed in many cells and tissues. We have found that the acute (1-2 h) stimulation of Glut 1-mediated glucose transport is controlled by "activation "' of Glut1 transporters pre-existing in the plasma membrane. We have also found that a fraction of cell Glut 1 is bound by stomatin resulting in inhibition of Glut1 function. More recently we have made the novel observation that a significant fraction of Glut1, and virtually all of stomatin, reside in the cholesterol- and sphingolipid-rich detergent-resistant membranes (DRMs), and that a fraction of Glut l (but not stomatin) moves out of the DRMs upon stimulation of glucose transport in response to inhibition of oxidative phosphorylation. Based on our results we propose that Glut 1 localized in the plasma membrane exists in two-states, namely inactive and active. This proposal will be tested by the following Specific Aims: 1) Test the hypothesis that association of stomatin and Glutl leads to inhibition of Glut1 function, 2) Test the hypothesis that Glutl dissociates from stomatin during its activation in response to inhibition of oxidative phosphorylation and following stimulation of AMP-activated protein kinase (AMPK), 3) Test the hypothesis that Glut l present in plasma membrane DRMs are palmitoylated and the movement of Glutl out of this micro-domain reflects its de-palmitoylation, and 4) Identify Glutl-binding proteins under basal and stimulated conditions. An understanding of the molecular events leading to control of Glut l function should provide new insights into potentially novel physiological and pharmacological regulators of this important transporter.

描述（由申请人提供）：GLUT1葡萄糖转运蛋白是一种积分的质膜蛋白，在许多细胞和组织中表达。我们发现，急性（1-2 h）刺激GLUT 1介导的葡萄糖转运受到质膜中存在的GLUT1转运蛋白的“激活”。我们还发现，细胞GLUT 1的一部分受阳性蛋白结合，从而抑制GLUT1功能。最近，我们对胆固醇和富含鞘脂的耐药膜（DRM）（DRMS）的大量glut1以及几乎所有的臭蛋白都进行了新的观察，几乎所有的凝血蛋白都存在，而Glut L（但不是臭头豆）的一小部分在刺激粘液量促进氧化量的刺激范围内将DRMS移出。根据我们的结果，我们提出，在两态中存在于质膜中的GLUT 1，即无活性和活性。 This proposal will be tested by the following Specific Aims: 1) Test the hypothesis that association of stomatin and Glutl leads to inhibition of Glut1 function, 2) Test the hypothesis that Glutl dissociates from stomatin during its activation in response to inhibition of oxidative phosphorylation and following stimulation of AMP-activated protein kinase (AMPK), 3) Test the hypothesis that Glut l present in质膜DRM被棕榈酰粘层，而从该微域中移动glutll，反映了其去甲状腺素，4）在基础和刺激的条件下鉴定出GLUTL结合蛋白。 对导致控制Glut L功能的分子事件的理解应为对该重要转运蛋白的潜在新型生理和药理调节剂提供新的见解。