Way CPY pathway Cvt pathway secretory CPY pathwayLeu, Cys/Gly Pro

Way CPY pathway Cvt pathway secretory CPY pathwayLeu, Cys/Gly Pro, Ala, Leu, Met, Phe, Tyr, Ser, Lys, Arg Xaa-Ala, Xaa-Pro-mannosidase 1 (Ams1), and aminopeptidase 4 (Ape4). Ape1 and Ams1 are resident vacuolar proteins, whereas Ape4 is cytosolic under physiological conditions, but targeted to the vacuole in a Cvt-dependent manner during nutrient starvation conditions.50 These substrates are synthesized in the cytoplasm, where they homooligomerize and bind to Atg19. Atg19 acts as a receptor for Cvt substrates.50-53 The autophagosomes associated with the Cvt pathway are smaller, and take approximately 10 times longer to form than those associated with autophagy.52,54 The Cvt pathway may be an important alternative trafficking mechanism to target vacuolar resident proteins that are otherwise damaging to secretory pathway residents. Alternatively, the Cvt pathway may facilitate transport of stable oligomeric proteins that are too large to traverse the vacuolar membrane via transporters. Finally, the Cvt pathway may facilitate vacuolar localization of membrane-associated proteins, such as Ams1, which lack a signal sequence to direct their translocation into the secretory pathway (Fig.Lutein 1).53 Endocytosis Protein composition at the cell surface is carefully regulated. Proteins that become damaged or that may be detrimental are removed by endocytosis and often traffic to the vacuole, where they are degraded.Ponatinib Plasma membrane-to-vacuole trafficking was first observed in yeast by monitoring lucifer yellow, a fluorescent dye that initially localizes to the cell surface but gradually accumulates in the vacuole after endocytosis.55 Subsequent genetic screens were instrumental in identifying components of the endocytic machinery,56-58 and more recently, cutting edge microscopy has generated a detailed temporal and spatial map of clathrin-mediated endocytosis (CME).59-62 CME is by far the best characterized endocytic pathway, requiring the orchestration of 50 proteins in yeast. The details of CME are the focus of many excellent recent reviews,63-66 but in brief this process is characterized by: 1) arrival of early endocytic and coat proteins, including Ede1, Syp1 and clathrin; 2) cargo recruitment, and the arrival of actin nucleation promoting factors, such as Pan1 and Las17, which is the WASP homolog; 3) regulated branched actin assembly by Arp2/3 and association of additional actin nucleationregulators, including Myo3 and Myo5; 4) membrane invagination, which is driven by actin polymerization and allows for recruitment of the amphiphysins Rvs161 and Rvs167 that aid in constricting the neck of the tubule; and 5) vesicle scission, which may involve the dynamin related protein Vps1, vesicle uncoating, and actin disassembly.PMID:35567400 59-61 It is important to note that the organization and timing of endocytic events described in yeast is now thought to be largely conserved in mammalian cells.67,68 In addition to the well-characterized CME pathway, a clathrinindependent endoctyic pathway (CIE), analogous to the RhoA CIE pathway in mammals, was also recently identified in yeast.69 Endocytosis and vacuolar sorting of cell surface proteins requires cargo ubiquitination. Pioneering studies of the yeast G-protein coupled receptors and nutrient permeases showed that ligand- or nutrient-induced ubiquitination precedes protein endocytosis.70-72 The ubiquitin ligase Rsp5 is required for ubiquitination,72-75 but most membrane cargos do not bind the ligase directly. Instead, a.