Cell surface membrane proteins play key roles in a broad range of physiological processes and form the largest class of approved drug targets. Despite this, fundamental questions regarding their regulation remain unanswered. My research focuses on the molecular mechanisms that govern intracellular trafficking of cell surface membrane proteins, particularly the recycling routes they use to return to the surface following internalization. To achieve this, we use a range of, cell biology, biochemistry and genetic approaches to understand how these protein machineries function.
We recently discovered a recycling pathway in yeast that returns membrane proteins to the surface via a route that appears not to involve a retrieval step at the Golgi apparatus. Genetic dissection of this pathway has revealed a large cohort of novel and conserved factors, including the Rag GTPases, which play a role in endosome to cell surface recycling1.
1. MacDonald C & Piper RC. Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases. Journal of Cell Biology (2017, accepted)
We have also developed a systematic library of ‘anti-ligase’ reagents, tools that can be used to identify the substrates of E3-ubiquitin ligase enzymes and the biological processes they regulate2.
2. MacDonald C, Winistorfer SC, Pope M, Wight ME, R. Piper RC. Enzyme reversal to explore the function of yeast E3 ubiquitin-ligases. Traffic (2017)
Mechanisms of cell surface recycling pathways
Funding body: Wellcome & The Royal Society