DENN domains at an interface of Rab signaling pathways

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The information encoded in the human genome is translated into proteins, which are the building blocks for cells and carry out all cellular activities. Certain classes of proteins are known as enzymes, which catalyze biochemical interactions. Through our NSERC funded research, we have recently identified a new class of enzymes, called GEFs that activate a member of a large family of proteins known as Rabs. Rabs are a type of cellular switch and are vital in turning on and turning off multiple cellular activities including cell growth and differentiation. However, the switches that turn on the Rabs are not well understood. There are 18 of the GEF proteins in humans and we think that each plays a role in the activation of Rabs. Moreover, and excitingly, these proteins also appear to act downstream of the activated Rab. Thus, we hypothesize that the GEF proteins are positioned between different Rab signaling pathways and this will be the focus of the research in this Discovery Grant application. If true, our studies will reveal a key new regulatory mechanism for controlling the vast Rab regulatory network in cells.