Garbage separation in the endoplasmic reticulum

Abstract

How does a cell distinguish between folded and misfolded proteins? Although it might be a while before we can answer this question, we do have a significant understanding about the disposal of misfolded proteins once they have been identified as garbage by the cell. In the secretory pathway, most ‘good’ proteins are sorted from the ‘bad’ at their site of biosynthesis and folding, the endoplasmic reticulum (ER). Conventional wisdom – supported by a plethora of data – has it that properly folded proteins are packaged into ER-to-Golgi transport vesicles, whereas misfolded proteins are retained in the ER and ultimately shunted back to the cytosol where they are degraded by proteasomes.