1. Academic Validation
  2. CHIP as a membrane-shuttling proteostasis sensor

CHIP as a membrane-shuttling proteostasis sensor

  • Elife. 2017 Nov 1;6:e29388. doi: 10.7554/eLife.29388.
Yannick Kopp 1 2 Wei-Han Lang 1 2 Tobias B Schuster 1 2 Adrián Martínez-Limón 1 2 Harald F Hofbauer 1 3 Robert Ernst 1 3 Giulia Calloni 1 2 R Martin Vabulas 1 2
Affiliations

Affiliations

  • 1 Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany.
  • 2 Institute of Biophysical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.
  • 3 Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract

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).

Keywords

cell biology; human; membrane; molecular chaperones; mouse; organelle; proteostasis; stress response; ubiquitin.

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