Model for Ere1 and Ere2 cargo-specific function in retromer-mediated recycling from endosomes. After stimulation, Can1 is internalized from the plasma membrane (PM) and delivered to early endosomes (EE). On early endosomes, a pool of Can1 is selected and sorted by the Snx4/41/42 complex for recycling to the Golgi and subsequent delivery back to the cell surface. Additional cargoes, such as the SNARE protein Snc1, are recycled from early endosomes in a retromer- and Ere1/Ere2–independent process. The remaining fraction of Can1 that is not recycled by the Snx4/41/42 complex is transported to late endosomes (LE). At late endosomes, Can1 is subject to different fates. First, Can1 is recognized by the Ere1/Ere2 complex for sorting into the retromer-mediated recycling pathway (see Discussion). The Ere1/Ere2 complex is not required for the sorting of additional retromer cargoes, such as Ftr1 and Vps10, into recycling tubules generated at late endosomes. Internalized Can1 that is not recycled by the Snx4/41/42 or retromer pathways is sorted into the ESCRT-mediated MVB pathway and eventually delivered to the vacuole for degradation.
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