The α-arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis

The regulation of nutrient uptake into cells is important, as it allows to either increase biomass for cell growth or to preserve homoeostasis. A key strategy to adjust cellular nutrient uptake is the reconfiguration of the nutrient transporter repertoire at the plasma membrane by the addition of nutrient transporters through the secretory pathway and by their endocytic removal. In this review, we focus on the mechanisms that regulate selective nutrient transporter endocytosis, which is mediated by the alpha-arrestin protein family. In the budding yeast Saccharomyces cerevisiae, 14 different alpha-arrestins (also named arrestin-related trafficking adaptors, ARTs) function as adaptors for the ubiquitin ligase Rsp5. They instruct Rsp5 to ubiquitinate subsets of nutrient transporters to orchestrate their endocytosis. The ART proteins are under multilevel control of the major nutrient sensing systems, including amino acid sensing by the general amino acid control and target of rapamycin pathways, and energy sensing by 5 '-adenosine-monophosphate-dependent kinase. The function of the six human alpha-arrestins is comparably under-characterised. Here, we summarise the current knowledge about the function, regulation and substrates of yeast ARTs and human alpha-arrestins, and highlight emerging communalities and general principles.

Automated summary

Regulating the endocytosis of nutrient transporters is crucial for maintaining homoeostasis and cell growth, with α-arrestin proteins mediating this process in yeast. While the function and regulation of yeast ARTs are well-studied, the role of human alpha-arrestins remains under-characterized.