TY  - JOUR
A1  - Kopp, Yannick
A1  - Lang, Wei-Han
A1  - Schuster, Tobias B.
A1  - Martínez-Limón, Adrián
A1  - Hofbauer, Harald F.
A1  - Ernst, Robert
A1  - Calloni, Giulia
A1  - Vabulas, Martin
T1  - CHIP as a membrane-shuttling proteostasis sensor
T2  - eLife
N2  - Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function. We reconstituted this process in vitro and found that mainly phosphatidic acid and phosphatidylinositol-4-phosphate enhance association of chaperone-free CHIP with liposomes. HSP70 and membranes compete for mutually exclusive binding to the tetratricopeptide repeat domain of CHIP. At new cellular locations, access to compartment-specific substrates would enable CHIP to participate in the reorganization of the respective organelles, as exemplified by the fragmentation of the Golgi apparatus (effector function).
KW  - Research article
KW  - Cell biology
KW  - Proteostasis
KW  - Molecular chaperones
KW  - Stress response
KW  - Ubiquitin
KW  - Organelle
KW  - Membrane
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44998
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-449985
SN  - 2050-084X
N1  - Copyright Kopp et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
VL  - 6
IS  - e29388
SP  - 1
EP  - 21
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -