Components and Mechanisms Involved in Protein Translocation Through the ER Membrane

Abstract

Many proteins are transported through the ER membrane as they are synthesized. These include secretory proteins and proteins of the plasma membrane, of lysosomes, and of all organelles of the secretory pathway. Synthesis of these proteins begins in the cytoplasm, but they are then targeted to the ER membrane by signal sequences, which are characterized by a stretch of at least six apolar amino acids, and which are often located at the amino terminus of precursor molecules. Recognition of the signal sequence and targeting of the nascent chain generally requires the function of the signal recognition particle (SRP) and of its membrane receptor (also called docking protein), but alternative targeting pathways exist. The targeting phase is followed by the actual translocation process. Proposed mechanisms of translocation have ranged from the idea that the transport of a polypeptide chain occurs directly through the phopholipid bilayer without participation of membrane proteins, to models according to which polypeptides are transported through a hydrophilic or amphiphilic channel formed from transmembrane proteins (for discussion, see Rapoport 1991). It now appears that a protein-conducting channel does exist. The evidence comes from electrophysiological data and from the identification of membrane proteins as putative channel constituents. The present paper summarizes our knowledge on the components involved in the actual translocation process. The mechanisms by which polypeptides are targeted to the ER membrane have been discussed elsewhere (Rapoport 1992).