Review

Histochemistry and Cell Biology

, Volume 129, Issue 2, pp 163-177

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Protein quality control: the who’s who, the where’s and therapeutic escapes

  • Jürgen RothAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich Email author 
  • , Gary Hin-Fai YamAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of ZurichDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, University Eye Centre
  • , Jingyu FanAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of ZurichDepartment of Biophysics, Peking University Health Science Center
  • , Kiyoko HiranoAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of ZurichThe Noguchi Institute
  • , Katarina Gaplovska-KyselaAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
  • , Valerie Le FournAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
  • , Bruno GuhlAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
  • , Roger SantimariaAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
  • , Tania TorossiAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
    • , Martin ZiakAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich
    • , Christian ZuberAffiliated withDivision of Cell and Molecular Pathology, Department of Pathology, University of Zurich Email author 

Abstract

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins.

Keywords

ERAD Protein folding disease Glucosidase II Glucosyltransferase EDEM1 Endomannosidase Chemical chaperones