Escaping the endoplasmic reticulum: why does a molecular chaperone leave home for greener pastures?

Abstract

© 2014 The Authors. Molecular chaperones reside in nearly every organelle within a eukaryotic cell, and in each of these compartments, they ensure that protein homeostasis (or proteostasis) is maintained. In this issue, Wiseman and colleagues find that an ER lumenal chaperone escapes this compartment when a specific stress pathway is activated. The chaperone, an Hsp40 homolog known as ERdj3, transits through the secretory pathway to the extracellular space. During this journey, ERdj3 can escort an aggregation-prone protein or it can identify aggregation-prone proteins extracellularly, thereby functioning outside of its normal environment. Selective secretion of an ER-resident chaperone upon activation of the unfolded protein response contributes to extracellular proteostasis.