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A Cure for Traffic Jams: Small Molecule Chaperones in the Endoplasmic Reticulum
Author(s) -
Römisch Karin
Publication year - 2004
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2004.00231.x
Subject(s) - endoplasmic reticulum , secretory protein , secretory pathway , biology , microbiology and biotechnology , osmolyte , stim1 , protein folding , biogenesis , calnexin , biochemistry , transport protein , chemical chaperone , unfolded protein response , secretion , golgi apparatus , calreticulin , gene
Folding in the endoplasmic reticulum is the limiting step for the biogenesis of most secretory pathway cargo proteins; proteins which fail to fold are initially retained in the endoplasmic reticulum and subsequently often degraded. Mutations that affect secretory protein folding have profound phenotypes irrespective of their direct impact on protein function, because they prevent secretory proteins from reaching their final destination. When unicellular organisms are stressed by fluctuation of temperature or ionic strength, they synthesize high concentrations of small molecules such as trehalose or glycerol to prevent protein denaturation. These osmolytes can also stabilize mutant secretory proteins and allow them to pass secretory protein quality control in the endoplasmic reticulum. Specific ligands and cofactors such as ions, sugars, or peptides have similar effects on specific defective proteins and are beginning to be used as therapeutic agents for protein trafficking diseases.