Genetic dissection of early endosomal recycling highlights a TORC1‐independent role for Rag GTPases

Abstract

Endocytosed cell surface membrane proteins rely on various recycling pathways for their return to the plasma membrane1. Although endosome‐to‐plasma membrane recycling is critical for many cellular processes2, much of the required machinery is unknown. We discovered that yeast also has a recycling route to the cell surface that bypasses the Golgi. Using an engineered synthetic reporter that exclusively follows this pathway, we performed a genetic screen to reveal a cohort of novel and conserved regulators of direct endosome to cell surface recycling. One critical component was the Rag GTPases, Gtr1 and Gtr2, which worked downstream of the exchange factor Vam6 and upstream of the Gtr1 effector Ltv1. Although the Rag GTPases are known to activate TORC1 on the vacuole/lysosome3–5, we find the Vam6>Gtr1‐Gtr2>Ltv1 recycling pathway is independent of TORC1, thus establishing a distinct role for these GTPases in early endosome recycling.Support or Funding InformationRO1GM058202