Using the yeast Saccharomyces cerevisiae to uncover regulatory mechanisms of cell surface membrane proteins

Membrane bound organelles define eukaryotic cells. Correct traffic of material between these organelles is crucial for proper cellular function. Arguably one of the most important membranes is the plasma membrane, separating the cell from its external environment. A cell must adapt and respond to its environment, which can change dramatically and rapidly. This is achieved through membrane trafficking mechanisms. The regulation of cell surface membrane proteins in their journey through trafficking pathways and within the plasma membrane itself is not fully understood. As many of these pathways and factors are conserved from yeast to humans, I used the yeast Saccharomyces cerevisiae as a model to uncover mechanistic details about how surface membrane proteins are regulated, with particular focus on cellular responses to nutrients. Following starvation, we detail how yeast cells upregulate endocytosis (Laidlaw et al., 2021) whilst simultaneously downregulating surface recycling (Amoiradaki et al., 2021; Laidlaw et al., 2022b) to drive degradation of surface membrane proteins. Curiously, not all nutrient transporters are degraded in response to starvation, with a small reserve pool being retained in special compartments of the plasma membrane termed eisosomes (Laidlaw et al., 2021). I went on to reveal that during starvation, eisosomes are regulated by dephosphorylation of its core structural subunit (Paine et al., 2022). Beyond this mechanistic work, I also set out to demystify trafficking pathways of surface proteins. I took advantage of the discovery that yeast cells grown in restricted uracil conditions rely on efficient trafficking of a uracil permease for efficient growth. This phenotype allowed me to perform a comprehensive genetic screen to identify and validate many known and novel candidate factors for surface protein trafficking (Paine et al., 2021). In combination, these discoveries represent a significant advance on our understanding of surface protein trafficking and will pave the way for many future studies, in both yeast and in cultured mammalian cell models.