Recycling of cell surface membrane proteins from yeast endosomes is regulated by ubiquitinated Ist1

Laidlaw et al. show nutrient transporters rapidly internalize to an early endosome population. Substrate withdrawal triggers endosomal recycling of transporters from endosomes back to the surface in a pathway that relies on ubiquitination of the ESCRT protein Ist1 and the associated factors Cdc48 and Npl4. Upon internalization, many surface membrane proteins are recycled back to the plasma membrane. Although these endosomal trafficking pathways control surface protein activity, the precise regulatory features and division of labor between interconnected pathways are poorly defined. In yeast, we show recycling back to the surface occurs through distinct pathways. In addition to retrograde recycling pathways via the late Golgi, used by synaptobrevins and driven by cargo ubiquitination, we find nutrient transporter recycling bypasses the Golgi in a pathway driven by cargo deubiquitination. Nutrient transporters rapidly internalize to, and recycle from, endosomes marked by the ESCRT-III associated factor Ist1. This compartment serves as both early and recycling endosome. We show Ist1 is ubiquitinated and that this is required for proper endosomal recruitment and cargo recycling to the surface. Additionally, the essential ATPase Cdc48 and its adaptor Npl4 are required for recycling, potentially through regulation of ubiquitinated Ist1. This collectively suggests mechanistic features of recycling from endosomes to the plasma membrane are conserved.

Automated summary

Laidlaw et al. demonstrate the mechanisms of nutrient transporter recycling, including substrate withdrawal-triggered endosomal recycling pathway and the regulatory role of ubiquitination. These mechanisms play a critical role in controlling the activity of surface membrane proteins.