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The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation

Title:

The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation

McNally, Erin Kate and Brett, Christopher Leonard (2018) The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation. Nature Communications, 9 (1). ISSN 2041-1723

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Official URL: http://dx.doi.org/10.1038/s41467-018-07734-5

Abstract

Surface receptor and transporter protein down-regulation is assumed to be exclusively mediated by the canonical multivesicular body (MVB) pathway and ESCRTs (Endosomal Sorting Complexes Required for Transport). However, few surface proteins are known to require ESCRTs for down-regulation, and reports of ESCRT-independent degradation are emerging, suggesting that alternative pathways exist. Here, using Saccharomyces cerevisiae as a model, we show that the hexose transporter Hxt3 does not require ESCRTs for down-regulation conferring resistance to 2-deoxyglucose. This is consistent with GFP-tagged Hxt3 bypassing ESCRT-mediated entry into intralumenal vesicles at endosomes. Instead, Hxt3-GFP accumulates on vacuolar lysosome membranes and is sorted into an area that, upon fusion, is internalized as an intralumenal fragment (ILF) and degraded. Moreover, heat stress or cycloheximide trigger degradation of Hxt3-GFP and other surface transporter proteins (Itr1, Aqr1) by this ESCRT-independent process. How this ILF pathway compares to the MVB pathway and potentially contributes to physiology is discussed.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Article
Refereed:Yes
Authors:McNally, Erin Kate and Brett, Christopher Leonard
Journal or Publication:Nature Communications
Date:2018
Funders:
  • Concordia Open Access Author Fund
  • NSERC grant RGPIN/ 403537-2011
  • NSERC grant RGPIN/2017-06652
Digital Object Identifier (DOI):10.1038/s41467-018-07734-5
ID Code:986011
Deposited By: KRISTA ALEXANDER
Deposited On:04 Oct 2019 19:47
Last Modified:04 Oct 2019 19:47
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