The cellular response to unfolded proteins: intercompartmental signaling.

Abstract

Both prokaryotic and eukaryotic cells respond to the accumulation of unfolded proteins by increasing the transcription of genes encoding molecular chaperones and other stress-responsive proteins. Different sets of genes are activated when particular cellular compartments are burdened with unfolded proteins. Cells thus maintain mechanisms to monitor changes in the concentration of unfolded proteins not only in the cytosol, but also in membrane-bound extracytoplasmic compartments. During the past year, work in yeast has identified a transmembrane receptor that appears to play a pivotal role in the regulation of protein folding. This receptor monitors the concentration of available chaperone molecules in the endoplasmic reticulum and transmits a signal to the cytosol to activate the transcription of nuclear genes encoding chaperones that are localized in the endoplasmic reticulum. Work using Escherichia coli suggests that prokaryotes also contain an intercompartmental 'unfolded protein' signaling pathway, in this case from the periplasmic space or outer membrane to the cytoplasm.