Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids
Vasyl Ivashov, Johannes Zimmer, Sinead Schwabl, Jennifer Kahlhofer, Sabine Weys, Ronald Gstir, Thomas Jakschitz, Leopold Kremser, Günther K. Bonn, Herbert Lindner, Lukas A. Huber, Sébastien Léon, Oliver Schmidt, David Teis
Abstract
broadly re-configures the nutrient transporters at the plasma membrane in response to amino acid availability, through endocytosis of sugar- and amino acid transporters (AATs) (Müller et al., 2015). A genome-wide screen now revealed that the selective endocytosis of four AATs during starvation required the α-arrestin family protein Art2/Ecm21, an adaptor for the ubiquitin ligase Rsp5, and its induction through the general amino acid control pathway. Art2 uses a basic patch to recognize C-terminal acidic sorting motifs in AATs and thereby instructs Rsp5 to ubiquitinate proximal lysine residues. When amino acids are in excess, Rsp5 instead uses TORC1-activated Art1 to detect N-terminal acidic sorting motifs within the same AATs, which initiates exclusive substrate-induced endocytosis. Thus, amino acid excess or starvation activate complementary α-arrestin-Rsp5-complexes to control selective endocytosis and adapt nutrient acquisition.