Signal sequence recognition and protein targeting to the endoplasmic reticulum membrane.

In this review, we attempt a timely survey of issues concerning protein translocation across the endoplasmic reticulum membrane, with a strong focus on the initial events that lead to the selection and proper delivery of proteins to this membrane system. Many new questions are raised by recent discoveries: it is now known that targeting can occur by multiple pathways and that the molecular machines that catalyze targeting and translocation are conserved in all cell types examined (from bacteria to mammalian cells). It is desirable to integrate the information from these different organisms into a coherent picture because we feel that the similarities-as well as the differences-found over such vast evolutionary distances will illuminate the fundamental principles that govern the inner workings of these components. Although this philosophy may cause an occasional oversimplification, we believe that it sets a useful conceptual framework to guide future experimental investigation. We focus here on recent developments and open questions, and do not intend this review to be comprehensive. Where appropriate, reference to more detailed reviews is given in the text.