Hatakeyama, Riko De Virgilio, Claudio 2019-10-01 Nutrient starvation induces the degradation of specific plasma membrane proteins through the multivesicular body (MVB) sorting pathway and of vacuolar membrane proteins through microautophagy. Both of these processes require the gateway protein Vps27, which recognizes ubiquitinated cargo proteins at phosphatidylinositol 3-phosphate-rich membranes as part of a heterodimeric complex coined endosomal sorting complex required for transport 0. The target of rapamycin complex 1 (TORC1), a nutrient-activated central regulator of cell growth, directly phosphorylates Vps27 to antagonize its function in microautophagy, but whether this also serves to restrain MVB sorting at endosomes is still an open question. Here, we show that TORC1 inhibits both the MVB pathway-driven turnover of the plasma membrane-resident high-affinity methionine permease Mup1 and the inositol transporter Itr1 and the microautophagy-dependent degradation of the vacuolar membrane-associated v- ATPase subunit Vph1. Using a Vps277D variant that mimics the TORC1- phosphorylated state of Vps27, we further show that cargo sorting of Vph1 at the vacuolar membrane, but not of Mup1 and Itr1 at endosomes, is sensitive to the TORC1-controlled modifications of Vps27. Thus, TORC1 specifically modulates microautophagy through phosphorylation of Vps27, but controls MVB sorting through alternative mechanisms. application/pdf https://folia.unifr.ch/global/documents/308146 https://folia.unifr.ch/documents/308146/files/vir_tsi.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1007/s00294-019-00982-y info:eu-repo/semantics/openAccess License undefined Current Genetics. - 2019, vol. 65, no. 5, p. 1243–1249 info:eu-repo/classification/udc/57 TORC1 specifically inhibits microautophagy through ESCRT-0 http://purl.org/coar/resource_type/c_6501