CHIP as a membrane-shuttling proteostasis sensor
- 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).
Author: | Yannick Kopp, Wei-Han Lang, Tobias B. Schuster, Adrián Martínez-Limón, Harald F. HofbauerORCiD, Robert Ernst, Giulia Calloni, Martin Vabulas |
---|---|
URN: | urn:nbn:de:hebis:30:3-449985 |
DOI: | https://doi.org/10.7554/eLife.29388 |
ISSN: | 2050-084X |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/29091030 |
Parent Title (English): | eLife |
Publisher: | eLife Sciences Publications |
Place of publication: | Cambridge |
Contributor(s): | Davis Ng |
Document Type: | Article |
Language: | English |
Year of Completion: | 2017 |
Date of first Publication: | 2017/11/01 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/12/19 |
Tag: | Cell biology; Membrane; Molecular chaperones; Organelle; Proteostasis; Research article; Stress response; Ubiquitin |
Volume: | 6 |
Issue: | e29388 |
Page Number: | 21 |
First Page: | 1 |
Last Page: | 21 |
Note: | 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. |
HeBIS-PPN: | 425780856 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Sondersammelgebiets-Volltexte | |
Licence (German): | Creative Commons - Namensnennung 4.0 |