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Rab-Effector-Kinase Interplay Modulates Intralumenal Fragment Formation during Vacuole Fusion.

Author(s): Karim MA, McNally EK, Samyn DR, Mattie S, Brett CL

Dev Cell. 2018 10 08;47(1):80-97.e6 Authors: Karim MA, McNally EK, Samyn DR, Mattie S, Brett CL

Article GUID: 30269949
The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation.

Author(s): McNally EK, Brett CL

Nat Commun. 2018 12 18;9(1):5358 Authors: McNally EK, Brett CL

Article GUID: 30560896
Title:The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation.
Authors:McNally EK,  Brett CL
Link:https://www.ncbi.nlm.nih.gov/pubmed/30560896?dopt=Abstract
DOI:10.1038/s41467-018-07734-5
Category:Nat Commun
PMID:30560896
Dept Affiliation: BIOLOGY
1 Department of Biology, Concordia University, 7141 Sherbrooke St. W., SP-501.15, Montréal, QC, H4R 1R6, Canada.
2 Department of Biology, Concordia University, 7141 Sherbrooke St. W., SP-501.15, Montréal, QC, H4R 1R6, Canada. christopher.brett@concordia.ca.

Description:

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

Nat Commun. 2018 12 18;9(1):5358

Authors: McNally EK, Brett CL

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.

PMID: 30560896 [PubMed - indexed for MEDLINE]