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...

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Bibliographic Details
Published in:eLife 2017-11, Vol.6
Main Authors: Kopp, Yannick, Lang, Wei-Han, Schuster, Tobias B, Martínez-Limón, Adrián, Hofbauer, Harald F, Ernst, Robert, Calloni, Giulia, Vabulas, R Martin
Format: Article
Language:English
Subjects:
Animals
Cell Biology
Cells, Cultured
Chaperones
Collaboration
Cytosol
Data analysis
Experiments
Fibroblasts
Fibroblasts - metabolism
Genes
Genetic aspects
Golgi apparatus
Heat shock proteins
Hsp70 protein
Humans
Life sciences
Ligases
Lipids
Liposomes
Localization
membrane
Membrane Proteins - metabolism
Membranes
Metabolism
Mice
Microscopy
molecular chaperones
organelle
Organelles
Organisms
Phosphates
Phosphatidic acid
Phospholipids
Post-transcription
Protein folding
Proteins
Proteostasis
Quality control
Statistical analysis
Stress response
Transcription
Transcription (Genetics)
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - metabolism
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Summary: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 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).
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.29388