A glucose-starvation response governs endocytic trafficking and eisosomal retention of surface cargoes in budding yeast

Abstract

ABSTRACT Eukaryotic cells adapt their metabolism to the extracellular environment. Downregulation of surface cargo proteins in response to nutrient stress reduces the burden of anabolic processes whilst elevating catabolic production in the lysosome. We show that glucose starvation in yeast triggers a transcriptional response that increases internalisation from the plasma membrane. Nuclear export of the Mig1 transcriptional repressor in response to glucose starvation increases levels of the Yap1801 and Yap1802 clathrin adaptors, which is sufficient to increase cargo internalisation. Beyond this, we show that glucose starvation results in Mig1-independent transcriptional upregulation of various eisosomal factors. These factors serve to sequester a portion of nutrient transporters at existing eisosomes, through the presence of Ygr130c and biochemical and biophysical changes in Pil1, allowing cells to persist throughout the starvation period and maximise nutrient uptake upon return to replete conditions. This provides a physiological benefit for cells to rapidly recover from glucose starvation. Collectively, this remodelling of the surface protein landscape during glucose starvation calibrates metabolism to available nutrients. This article has an associated First Person interview with the first author of the paper.