Coordination of phosphoinositides and RAB GTPases in membrane trafficking events

膜运输事件中磷酸肌醇和 RAB GTP 酶的协调

• 批准号: RGPIN-2016-03730
• 负责人: Jean, Steve
• 金额: $ 2.62万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=654565
• 关键词: Coordination; phosphoinositides; RAB; GTPases; membrane

Every cells of our body are composed of multiple types of compartments, all segregated from each other's. These compartments, called organelles and vesicles, are delimitated by membranes. These membranes are highly controlled and the mechanisms regulating them are collectively named ‘membrane trafficking' events. Significantly, these organelles and vesicles exchange a lot of material. Since, they mix together through the exchange of material, molecular mechanisms are required to control and maintain their identities. One could compare the exchange of material between organelles as mixing different colors of Play-Doh. If no precautions are taken, then over time, the Play-Doh will turn brown since all colors will be mixed. In our cells, two major classes of membrane identity regulators were identified, and are called RAB GTPases and phosphoinositides. The action of both maintains compartment distinctiveness, and allows the different organelles and vesicles to exchange material and maintain their identities. From the Play-Doh analogy, one could compare RABs and phosphoinositides to brushes and different colors of paint. Studies have found that RABs and phosphoinositides work together, like a brush needs paint. Surprisingly, it was shown in cells that a phosphoinositide made by different processes affects the function of a RAB in various manners. In the Play-Doh example, we could compare it to different white colors from different companies sticking more or less to a brush. As such, although all the paints are white, they won't have the same effect on the Play-Doh.***Our work will characterize how RABs and phosphoinositides work molecularly in cells. Briefly, and based on the Play-Doh analogy, we will identify why different white paints acts differently. To do so, we will use a new technique that will complement previous studies. As such, we will identify all the components in the brush required for 'binding' to the white paint and to transfer it to the Play-Doh. Secondly, once identified we will very specifically remove single components of the white paints from different companies, and in that context, we will monitor how the paint binds to the brush and how it now affects the Play-Doh.***Altogether, our studies will define the molecular coordination between regulators of membrane traffic. Our work will shed light on an important regulatory process occurring in all our cells. Moreover, the data gained from our studies will benefit other researchers and help them in their own work.**

我们身体的每一个细胞都是由多种类型的隔间组成的，所有这些隔间都是相互隔离的。这些隔室被称为细胞器和囊泡，由膜界定。这些膜是高度受控的，调节它们的机制统称为“膜运输”事件。值得注意的是，这些细胞器和囊泡交换了大量的物质。由于它们通过物质交换混合在一起，因此需要分子机制来控制和保持它们的身份。人们可以将细胞器之间的物质交换比作混合不同颜色的培乐多。如果不采取预防措施，那么随着时间的推移，橡皮泥会变成棕色，因为所有的颜色都会混合。在我们的细胞中，确定了两种主要类型的膜身份调节剂，称为RAB GTP酶和磷酸肌醇。两者的作用保持了区室的独特性，并允许不同的细胞器和囊泡交换物质并保持其身份。从培乐多的类比中，人们可以将RAB和磷酸肌醇比作画笔和不同颜色的油漆。研究发现，RAB和磷酸肌醇一起工作，就像画笔需要油漆一样。令人惊讶的是，在细胞中显示，由不同过程产生的磷酸肌醇以各种方式影响RAB的功能。在培乐多的例子中，我们可以将其与来自不同公司的不同白色颜色进行比较，这些颜色或多或少地粘在刷子上。因此，虽然所有的油漆都是白色的，但它们不会对培乐多产生同样的效果。我们的工作将描述RAB和磷酸肌醇在细胞中的分子工作方式。简单地说，根据培乐多的类比，我们将确定为什么不同的白色油漆的行为不同。为此，我们将使用一种新技术来补充以前的研究。因此，我们将确定画笔中“绑定”到白色油漆并将其转移到培乐多所需的所有组件。其次，一旦确定，我们将非常明确地删除来自不同公司的白色油漆的单一成分，在这种情况下，我们将监测油漆如何与刷子结合，以及它现在如何影响培乐多。总之，我们的研究将确定膜交通调节剂之间的分子协调。我们的工作将揭示发生在我们所有细胞中的重要调控过程。此外，从我们的研究中获得的数据将使其他研究人员受益，并帮助他们自己的工作。