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Cells lacking Snx4/41/42, retromer components, Ere1, or Ere2 are resistant to canavanine. (A) Model for Can1 trafficking and the screen for recycling mutants. In wild-type cells, the lifetime of Can1 at the PM is regulated by endocytosis, recycling, and degradation (left). In mutant cells deficient for Can1 recycling, Can1 cell-surface levels are reduced, resulting in reduced uptake of the toxic arginine analogue canavanine (squares). (B) Classification of cvr mutants identified in the canavanine resistance screen. (C) Cells impaired in endosomal recycling are resistant to canavanine. Serial dilutions (fourfold) of wild-type (WT) and deletion mutant cells (as indicated) were grown on synthetic media plates with or without 2 μg/ml canavanine for 2 d at 26°C. (D) Schematic diagrams for Ere1, Ere2, and their human orthologues WDR85 and WDR6, respectively.