Figure 18 An overview of protein localisation in eukaryotes. (a) During translation, all protein synthesis is initiated on a free ribosome in the cytosol. The N-terminus of the protein (denoted NH2 here) emerges from the ribosome. (b) In the absence of an RER localisation signal sequence, translation continues on the free ribosome and the polypeptide is released into the cytosol once translation is complete. It may then be post-translationally relocated to somewhere else in the cell. (c) The presence of a specific RER signal sequence at the beginning of the polypeptide directs binding of the whole ribosome-mRNA-polypeptide complex to the RER membrane. The polypeptide chain is synthesised across the RER membrane and into the RER lumen (cotranslational localisation). (d) Transmembrane proteins are retained in the RER membrane by alternating translocation start-transfer and stop-transfer sequences that thread the polypeptide through the membrane in sections.