The Signal Recognition Particle and Its Receptor in ER Protein Targeting

The complex mechanisms that regulate cotranslational targeting of proteins to the endoplasmic reticulum (ER) begin with the translation of a signal sequence in the nascent protein that encodes the required targeting information. In eukaryotes, the recognition and correct sorting of signal sequence-containing polypeptides involves a relatively complicated seven-component ribonucleoprotein complex termed signal recognition particle (SRP) and an ER membrane-bound SRP receptor (SR), a heterodimer composed of two unusual GTPases. The orchestration of these and other components involved in the targeting of proteins to the ER are described in this chapter. The discovery and elucidation of this pathway is presented from a historical perspective that focuses on what is known about SRP and SR. However, to fully explain cotranslational protein targeting requires analysis of the signal hypothesis, mRNA partitioning and alternate mechanisms regulating targeting of the nascent polypeptide chain. Attempts to analyze the structure of the components involved have met with considerable success and the challenge ahead involves making use of this data to extend our understanding of the activity and composition of the ER-directed protein targeting machinery. © 2007 Elsevier Inc. All rights reserved.