Regulation of endosome function by the AAA-ATPase Vps4

细胞对来自环境的许多信号作出反应。一些信号告诉细胞生长和分裂，另一些信号告诉细胞休息。这些信号在健康细胞中通常处于平衡状态。为了防止细胞以不受控制的方式生长和分裂并形成癌症，有一些机制可以关闭生长信号。一种机制是破坏负责生长信号的蛋白质。这包括将信号蛋白从发生信号的细胞膜一侧翻转（通过一种称为多泡体（MVB）分选的过程）到不能发生信号的另一侧，以及信号蛋白可以被降解的另一侧。有趣的是，最近发现一些病毒（包括艾滋病病毒）使用相同的MVB分选机制从被感染的细胞中逃脱。然而，病毒没有经过MVB分选进入内部隔室并被降解，而是能够使用相同的机制翻转出细胞。MVB分选是如何发生的尚不清楚，但其机制在进化过程中是保守的，甚至像酵母这样的微生物也可以对蛋白质进行MVB分选。我们正在研究被称为Vps4的MVB分选机制的一个组成部分，它存在于人类细胞和酵母细胞中。由于人类Vps4和酵母Vps4似乎以相同的方式起作用，并且由于强大的分子遗传学方法可以用于酵母来阐明蛋白质的功能（其中一些是不可能在人类细胞中实现的），我们正在使用酵母来研究Vps4的功能。一旦我们了解了酵母的Vps4是如何工作的，我们就能测试人类的Vps4是否也以同样的方式工作。了解MVB分选机制将使我们了解细胞如何防止不受控制的生长和分裂，也可能帮助我们找到预防艾滋病感染的方法。

Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signalling protein from one side of the membrane where signalling occurs to the other side where signalling cannot occur and where the signalling protein can be degraded. Interestingly, it has recently been discovered that some viruses (including the AIDS virus) use the same MVB sorting mechanisms to escape from infected cells. Instead of undergoing MVB sorting into an internal compartment and getting degraded, however, the virus is able to use the same mechanism to flip out of the cell. How MVB sorting occurs is not known, but the mechanism has been conserved through evolution and even microbes like yeast can perform MVB sorting of proteins. We are investigating a component of the MVB sorting mechanism known as Vps4 which is present in both human cells and in yeast cells. Since the human Vps4 and yeast Vps4 seem to function in the same way, and since powerful molecular genetic approaches can be used in yeast to elucidate how proteins function (some of which are not possible with human cells), we are using yeast to investigate Vps4 function. Once we understand how the yeast Vps4 works, we will be able to test if human Vps4 works the same way. Understanding the MVB sorting mechanism will give us information on how cells prevent uncontrolled growth and division and may also help us find ways of preventing AIDS infection.