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

Chris MacDonald; Robert C Piper

doi:10.1083/jcb.201702177

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

Journal article

Open access

Peer reviewed

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

Chris MacDonald and Robert C Piper

The Journal of cell biology, Vol.216(10), pp.3275-3290

10/02/2017

DOI: 10.1083/jcb.201702177

PMCID: PMC5626546

PMID: 28768685

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Abstract

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 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.

Adaptor Proteins, Vesicular Transport - genetics

Adaptor Proteins, Vesicular Transport - metabolism

Endosomes - genetics

Endosomes - metabolism

Guanine Nucleotide Exchange Factors - genetics

Guanine Nucleotide Exchange Factors - metabolism

Mechanistic Target of Rapamycin Complex 1

Monomeric GTP-Binding Proteins - genetics

Monomeric GTP-Binding Proteins - metabolism

Multiprotein Complexes - metabolism

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae - metabolism

Saccharomyces cerevisiae Proteins - genetics

Saccharomyces cerevisiae Proteins - metabolism

TOR Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases
Creators: Chris MacDonald - University of Iowa
Robert C Piper - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.216(10), pp.3275-3290
DOI: 10.1083/jcb.201702177
PMID: 28768685
PMCID: PMC5626546
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Grant note: P30 CA086862 / NCI NIH HHS R01 GM058202 / NIGMS NIH HHS
Language: English
Date published: 10/02/2017
Academic Unit: Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
Record Identifier: 9984297495802771

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