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

TY - JOUR

T1 - Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases

AU - MacDonald, Chris

AU - Piper, Robert C

N1 - This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2017/8/2

Y1 - 2017/8/2

N2 - Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface.

AB - Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface.

KW - Adaptor Proteins, Vesicular Transport/genetics

KW - Endosomes/genetics

KW - Guanine Nucleotide Exchange Factors/genetics

KW - Mechanistic Target of Rapamycin Complex 1

KW - Monomeric GTP-Binding Proteins/genetics

KW - Multiprotein Complexes/metabolism

KW - Saccharomyces cerevisiae Proteins/genetics

KW - Saccharomyces cerevisiae/genetics

KW - TOR Serine-Threonine Kinases/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85030213042&partnerID=8YFLogxK

U2 - 10.1083/jcb.201702177

DO - 10.1083/jcb.201702177

M3 - Article

C2 - 28768685

SN - 0021-9525

VL - 216

SP - 3275

EP - 3290

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 10

ER -