CHIP as a membrane-shuttling proteostasis sensor

• Published in: eLife 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: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 01.11.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• 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; Massachusetts; Germany; mouse; cell biology; membrane; stress response; organelle; molecular chaperones; proteostasis; human; ubiquitin
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.29388

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).