The signal sequence of the p62 protein of Semliki Forest virus is involved in initiation but not in completing chain translocation

IOSYNTHESIS of proteins at the ER can be subdivided into several steps. These are (a) targeting of translation complexes to the ER membrane; (b) synthesis and transfer (translocation) of the polypeptide chain across the lipid bilayer; and (c) protein maturation in the lumen of ER (chain folding, disulphide bridge formation, glycosylation, and oligomerization). The mechanisms for these processes have been studied extensively during recent years (Kornfeld and Kornfeld, 1985; Wickner and Lodish, 1985; Rapoport, 1986; Lodish, 1988; Rothman, 1989) . A most important finding has been that all proteins made at the ER carry a signal sequence (also called signal peptide), a hydrophobic peptide which is usually located at the NH2-terminal region of the polypeptide chain. One function of the signal peptide is to achieve targeting of the polysome to the ER membrane (Rapoport, 1986) . When the signal sequence emerges from the ribosome it binds to the signal recognition particle, which mediates binding of the polysome to the docking protein in the ER. After this another function of the signal sequence is expressed, that is to interact with some components of the ER membrane and thereby initiate translocation of the polypeptide chain into the lumen of the ER (Gilmore and Blobel, 1985; Robinson et al., 1987; Wiedmann et al., 1987) . Further synthesis of the polypeptide then continues with concomitant chain translocation. An important but as yet unresolved question is whether the signal sequence has any role in the translocation process per se or whether its functions are limited to the targeting and translocation-initiation steps. For instance, Singer and co-workers Danny Huylebroeck's present address is Innogenetics, Industriepark 7, Box 4, B-9710, Ghent, Belgium.