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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743419
• 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.

我们身体的每个细胞都由多种类型的隔室组成，所有细胞都与彼此隔离。这些称为细胞器和囊泡的隔室被膜界定。这些膜是高度控制的，调节它们的机制被统称为膜贩运事件。值得注意的是，这些细胞器和囊泡交换了许多材料。由于它们通过材料交换混合在一起，因此需要分子机制来控制和维持其身份。一个人可以将细胞器之间的材料交换与混合不同的游戏颜色。如果没有采取预防措施，那么随着时间的流逝，Play-Doh会变成棕色，因为所有颜色都会混合在一起。在我们的细胞中，确定了两种主要类别的膜身份调节剂，称为RAB GTPase和磷酸肌醇。两者的作用都保持着独特的范围，并允许不同的细胞器和囊泡交换材料并保持其身份。从Play-Doh类比来看，可以将Rabs和Phoshoinositides与刷子和不同颜色的油漆进行比较。研究发现，RABS和磷酸肌醇可以像刷子需要油漆一样一起使用。令人惊讶的是，在细胞中表明，由不同过程产生的磷酸肌醇会影响Rab以各种方式的功能。在Play-Doh示例中，我们可以将其与不同的公司或多或少地与刷子相提并论的不同白色。因此，尽管所有油漆都是白色的，但它们对游戏的影响不会相同。我们的工作将表征兔和磷酸肌醇在细胞中的分子作用。简而言之，根据Play-Doh的类比，我们将确定为什么不同的白色油漆的作用不同。为此，我们将使用一种新技术，可以补充以前的研究。因此，我们将确定“绑定”到白色油漆所需的刷子中的所有组件，并将其转移到游戏中。其次，一旦确定，我们将非常具体地删除来自不同公司的白色油漆的单个组件，在这种情况下，我们将监视油漆如何与刷子结合，以及它如何影响Play-Doh。我们的工作将阐明我们所有细胞中发生的重要调节过程。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。