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Transmembrane domain quality control systems operate at the endoplasmic reticulum and Golgi apparatus

Briant, K; Johnson, N; Swanton, E; (2017) Transmembrane domain quality control systems operate at the endoplasmic reticulum and Golgi apparatus. PLoS ONE , 12 (4) , Article e0173924. 10.1371/journal.pone.0173924. Green open access

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Abstract

Multiple protein quality control systems operate to ensure that misfolded proteins are efficiently cleared from the cell. While quality control systems that assess the folding status of soluble domains have been extensively studied, transmembrane domain (TMD) quality control mechanisms are poorly understood. Here, we have used chimeras based on the type I plasma membrane protein CD8 in which the endogenous TMD was substituted with transmembrane sequences derived from different polytopic membrane proteins as a mode to investigate the quality control of unassembled TMDs along the secretory pathway. We find that the three TMDs examined prevent trafficking of CD8 to the cell surface via potentially distinct mechanisms. CD8 containing two distinct non-native transmembrane sequences escape the ER and are subsequently retrieved from the Golgi, possibly via Rer1, leading to ER localisation at steady state. A third chimera, containing an altered transmembrane domain, was predominantly localised to the Golgi at steady state, indicating the existence of an additional quality control checkpoint that identifies non-native transmembrane domains that have escaped ER retention and retrieval. Preliminary experiments indicate that protein retained by quality control mechanisms at the Golgi are targeted to lysosomes for degradation.

Type: Article
Title: Transmembrane domain quality control systems operate at the endoplasmic reticulum and Golgi apparatus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0173924
Publisher version: http://doi.org/10.1371/journal.pone.0173924
Language: English
Additional information: Copyright: © 2017 Briant et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Membrane proteins, Golgi apparatus, Quality control, Small interfering RNAs, Lysosomes, Integral membrane proteins, Immunoblotting, Endoplasmic reticulum
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1556398
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