ABSTRACT
T he endoplasmic reticulum (ER ) is the exclusive site o f secretory and integral membrane protein synthesis. The process o f com partm entalizing protein synthesis to the E R occurs through a positive selection mechanism, the signal recognition particle (SR P) pathway. Growing evidence indicates the E R membrane may also be a m ajor site o f synthesis for cytosolic and nucleoplasmic proteins. This idea is highlighted by the finding o f substantial overlap in m R N A com position o f free and membrane-bound polyribosomes. H ow m R N A s encoding proteins that lack signal peptides would be targeted to the E R for translation is not known. In the context o f current models, the synthesis o f cytosolic proteins on the E R raises a number o f intriguing questions regarding the biological function(s) o f protein synthesis compartmentalization. Given the overlap in the identities o f m R N A s present in the cytosol and E R membrane populations, it is not known i f there are selective advantages in targeting particular m R N A s to one compartment versus the other. Recent studies indicate cytosolic and ER-bound ribosomes translate m R N A s with distinct kinetics; E R ribosomes display 3-4-fold higher levels o f protein synthesis than soluble ribosomes. Potentially, directingm RN As to the E R for translation may function to increase the relative protein expression. Additionally, studies o f cell stress pathways have revealed a bias in the cells utilization o f the E R for synthesis o f key stress response (nucleoplasmic) proteins. Em erging from these data is a broadening role for the E R membrane as a key site for global protein synthesis regulation.
