Coordination of phosphoinositides and RAB GTPases in membrane trafficking events

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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.