Figure 5.

Models for escape of ER proteins from retention. We propose that escape of ER proteins from retention requires ongoing protein synthesis and that escape is only possible for newly synthesized ER proteins. We hypothesize that the initial localization process is driven by retention (or retrieval) signals, e.g., KDEL and lys-lys-X-X and their cognate receptors, which may be diminished in number or alternatively may be functionally compromised in immature thymocytes as a result of posttranslational modifications, association with other proteins, etc. However, once nascent molecular chaperones have been bound by retention/retrieval receptors they are permanently held within the ER, possibly by protein:protein interactions independent of the retention signals.