FIGURE 2: Regulation of amino acid transporter endocytosis by nutrient stress. During energy sufficiency the arrestin-like adaptor Art1 recruits the ubiquitin ligase Rsp5 to the plasma membrane to induce the ubiquitination of the arginine transporter Can1. Subsequent endocytosis of Can1 limits amino acid uptake. This pathway is regulated by the central nutrient sensor mTORC1 which in its active state keeps the negative regulator of Art1, the kinase Npr1, inactive. During starvation mTORC1 is rendered inactive so that Npr1 can inhibit Art1 via phosphorylation. Consequently, Can1 is not ubiquitinated by Rsp5 and remains at the plasma membrane to increase arginine uptake (see section ”Endocytosis and nutrient signaling” for further details). CCV, clathrin-coated vesicle; EE, early endosome; RE, recycling endosome; LE, late endosome.