| First Author | Kopp Y | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 29091030 | Mgi Jnum | J:380781 |
| Mgi Id | MGI:8292971 | Doi | 10.7554/eLife.29388 |
| Citation | Kopp Y, et al. (2017) CHIP as a membrane-shuttling proteostasis sensor. Elife 6:e29388 |
| abstractText | 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). |
