Protein transport across the endoplasmic reticulum membrane: facts, models, mysteries.

The first step in the biosynthesis of secretory proteins, plasma membrane proteins, and many other proteins in a eukaryotic cell involves the transport of at least portions of the polypeptides across the endoplasmic reticulum (ER) membrane. Parts of the polypeptide chains serve as signals that direct the translocation across and the integration into the ER membrane and also determine the orientation of membrane proteins. The transport process itself may be divided into two phases: an initiation or targeting cycle, which is fairly well understood, and the actual transfer of the polypeptide chain through the membrane, the mechanism of which is still mysterious. The initiation cycle generally involves the function of the signal recognition particle (SRP) which binds to signal sequences through its 54-kDa polypeptide component, and of the SRP-receptor (docking protein) in the ER membrane whose function is dependent on GTP. The membrane transfer of the polypeptide chain appears to involve a translocation complex consisting of several membrane proteins, one of which is the signal sequence receptor protein (SSR).