ABSTRACT
C urrent estimates suggest that 20-30% o f a typical eukaryotic genome encodes proteins that span a membrane, the m ajority o f which are generated at the endoplasmic reticulum (ER). A remarkable proteinaceous complex em bedded in the membrane o f the ER , termed the E R translocon, is responsible for both the transport o f water-soluble proteins from the cytosol into the E R lumen and for the incorporation o f membrane proteins into the lipid bilayer. O nce synthesised, proteins may be trafficked from the E R to their final subcellular locations or secreted from the cell. Thus, for many soluble proteins, the E R marks the entry point into the secretory pathway and the site at which significant and essential m odifications to the structure o f the protein are carried out. W hilst some o f the basic principals underlying the biosynthesis o f integral membrane proteins are similar to those for soluble proteins, membrane protein biosyn thesis is com plicated by the presence o f one or more membrane-spanning regions. This review will focus on our current understanding o f translocon-mediated membrane protein integration at the m ammalian ER , with a particular emphasis on the biogenesis o f complex polytopic proteins with multiple transmembrane (T M ) segments.
