Protein quality control: the who's who, the where's and therapeutic escapes.
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.
Roth
Jürgen
J
Division of Cell and Molecular Pathology, Department of Pathology, University of Zurich, 8091 Zurich, Switzerland. jurgen.roth@bluewin.ch
Yam
Gary Hin-Fai
GH
Fan
Jingyu
J
Hirano
Kiyoko
K
Gaplovska-Kysela
Katarina
K
Le Fourn
Valerie
V
Guhl
Bruno
B
Santimaria
Roger
R
Torossi
Tania
T
Ziak
Martin
M
Zuber
Christian
C
D015195:Drug Design; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008661:Metabolism, Inborn Errors / Q000188:drug therapy / Q000209:etiology; D018832:Molecular Chaperones / Q000378:metabolism* / Q000627:therapeutic use; D017510:Protein Folding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
C486654:EDEM1 protein, human; D008565:Membrane Proteins; D018832:Molecular Chaperones; D011506:Proteins