Counting functional IP3 receptors into the plasma membrane

计算质膜中的功能性 IP3 受体

• 批准号: BB/E004660/1
• 负责人: Colin Taylor
• 金额: $ 40.87万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE004660%2F1
• 关键词: Counting; functional; IP3; receptors; into

The protective membrane that surrounds every cell provides the barrier needed to allow each cell to maintain a composition different from that of its environment, but it also isolates the cell interior from important extracellular signals. The latter problem is resolved by inserting proteins into the membrane that specifically recognise extracellular signals and then transduce them into intracellular signals capable of controlling cellular activity. Ca is the most important of these intracellular signals, not least because it is present at much lower concentration within the cell than on the opposite side of the membranes that either surround the cell or the organelles within it. The opening of Ca channels within these membranes is the most common means whereby extracellular stimuli evoke an increase in intracellular Ca concentration. For many years we have known that IP3 receptors are the most important and widely expressed Ca channels within the membranes of intracellular stores, but our recent work suggests that they are also functionally expressed in the membrane (PM) that surrounds the cell, where they provide the route for much of the Ca that flows into the cell from outside. To our great surprise, each cell absolutely reliably counts 1-3 IP3R into the PM from the many 1000s expressed within the cell. Such counting is important because otherwise IP3R in the PM might cause the cell to be overwhelmed with Ca and that would be toxic. But how can a cell so reliably count so few proteins into the membrane surrounding each cell? This project aims to answer that question.

围绕每个细胞的保护膜提供了允许每个细胞保持与其环境不同的组成所需的屏障，但它也将细胞内部与重要的细胞外信号隔离开来。后一个问题是通过将蛋白质插入细胞膜来解决的，这些蛋白质特异性地识别细胞外信号，然后将它们转化为能够控制细胞活性的细胞内信号。Ca是这些细胞内信号中最重要的，尤其是因为它在细胞内的浓度比在围绕细胞或细胞器的膜的相对侧低得多。这些膜内Ca通道的开放是细胞外刺激引起细胞内Ca浓度增加的最常见手段。多年来，我们已经知道IP 3受体是细胞内储存膜内最重要和最广泛表达的Ca通道，但我们最近的工作表明，它们也在细胞周围的膜（PM）中功能性表达，它们为从外部流入细胞的大部分Ca提供了途径。令我们非常惊讶的是，每个细胞绝对可靠地从细胞内表达的1000个中将1-3个IP 3R计数到PM中。这种计数是重要的，因为否则PM中的IP 3R可能导致细胞被Ca淹没，这将是有毒的。但是，一个细胞如何能够如此可靠地将如此少的蛋白质计数到每个细胞周围的膜中呢？这个项目旨在回答这个问题。

项目成果

Regulation of inositol 1,4,5-trisphosphate receptors by cAMP independent of cAMP-dependent protein kinase.

• DOI: 10.1074/jbc.m109.096016
• 发表时间: 2010-04-23
• 期刊: The Journal of biological chemistry
• 作者: Tovey SC;Dedos SG;Rahman T;Taylor EJ;Pantazaka E;Taylor CW
• 通讯作者: Taylor CW

Functional ryanodine receptors in the plasma membrane of RINm5F pancreatic beta-cells.

• DOI: 10.1074/jbc.m805587200
• 发表时间: 2009-02-20
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Rosker, Christian;Meur, Gargi;Taylor, Emily J. A.;Taylor, Colin W.
• 通讯作者: Taylor, Colin W.

Synthetic partial agonists reveal key steps in IP3 receptor activation.

• DOI: 10.1038/nchembio.195
• 发表时间: 2009-09
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Rossi, Ana M.;Riley, Andrew M.;Tovey, Stephen C.;Rahman, Taufiq;Dellis, Olivier;Taylor, Emily J. A.;Veresov, Valery G.;Potter, Barry V. L.;Taylor, Colin W.
• 通讯作者: Taylor, Colin W.