Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains

Significance The plasma membrane of eukaryotic cells is compartmentalized into domains enriched in specific lipids and proteins. However, our understanding of the mechanisms and functions of this lateral segregation remains incomplete. Here, we show that the clustering of the yeast Can1 arginine transporter into domains is dictated by its conformation and requires sustained biogenesis of complex sphingolipids. Furthermore, this clustering confers to Can1 and other transporters protection from ubiquitin-dependent endocytosis. Under nutrient-starvation conditions, this protective role is reinforced, thereby allowing cells to preserve a fraction of their nutrient transporters from bulk endocytosis and to more efficiently resume growth when replenishing compounds are available. Our study reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains.