Counting functional IP3 receptors into the plasma membrane

包围着每个细胞的保护膜提供了使每个细胞保持与其环境不同的成分所需的屏障，但它也将细胞内部与重要的细胞外信号隔离开来。后一个问题的解决方法是将识别细胞外信号的蛋白质插入细胞膜，然后将其转化为能够控制细胞活动的细胞内信号。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围绕细胞或细胞内细胞器的膜的相反一侧低得多。这些膜内钙通道的开放是细胞外刺激引起细胞内钙浓度增加的最常见的手段。多年来，我们已经知道IP3受体是细胞内储存膜内最重要和最广泛表达的钙通道，但我们最近的工作表明，它们也在细胞周围的膜(PM)上功能性地表达，在那里它们为许多从外部流入细胞的钙提供了途径。令我们非常惊讶的是，每个细胞都绝对可靠地从细胞内表达的1000个IP3R中将1-3个IP3R计入PM。这样的计数很重要，因为否则PM中的IP3R可能会导致细胞内钙超载，这将是有毒的。但是，一个细胞如何能如此可靠地将如此少的蛋白质计数到每个细胞周围的膜上呢？这个项目旨在回答这个问题。

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.