the endoplasmic reticulum or ER is the most extensive membrane system in eukaryotic cells proteins transported to the GGI apparatus endosomes lomes and the cell surface all must first enter the ER from the cytool as an mRNA molecule is translated into a protein many ribosomes bind to it forming a poly ribosome there are two separate populations of poly ribosomes in the cytool that share the same pool of ribosomal subunits free ribosomes are unattached to any membrane membranebound ribosomes become riveted to the ER membrane and translate proteins that are translocated into the ER these membrane bound ribosomes coat the surface of the ER creating regions called rough endoplasmic reticulum two kinds of proteins are moved from the cytool to the ER water soluble proteins completely cross the ER membrane and are released into the lumen while transmembrane proteins only partially cross the ER and become embedded in the membrane all these proteins are directed to the ER by a signal sequence of small hydrophobic amino acids the signal sequence is guided to the ER membrane with a signal recognition particle or SRP which binds the ER signal sequence in the new protein as it emerges from the ribosome protein synthesis then slows down until the SRP ribosome complex binds to an SRP receptor in the ER membrane the SRP is then released passing the ribosome to a protein translocation channel in the ER membrane thus the SRP and SRP receptor function as molecular matchmakers connecting ribosomes that are synthesizing proteins containing ER signal sequences to available ER translocation channels in addition to directing proteins to the ER the signal sequence functions to open the translocation channel the signal peptide remains bound to the channel while the rest of the protein chain is threaded through the membrane as a large loop once the protein has passed through the membrane it is released into the ER Lumin after the signal sequence has been cleaved off by a signal peptidase located on the luminal side of the ER membrane the signal peptide is then released from the translocation channel into the membrane and rapidly degraded it is thought that a protein serving as a plug then binds from the ER Lumen to close the inactive Channel but not all proteins that enter the ER are released into the ER Lumen some remain embedded in the ER membrane as transmembrane proteins for clarity's sake the membrane bound ribosome will be omitted to illustrate the translocation of transmembrane proteins into the ER membrane in the simplest case that of a transmembrane protein with a single membrane spanning segment the N terminal signal sequence initiates translocation just as for a soluble protein but the transfer process is halted by an additional sequence of hydrophobic amino acids a stop transfer sequence further in the polypeptide chain the stop transfer sequence is released laterally from the translocation Channel and drifts into the plane of the lipid bilayer where it forms a membrane spanning segment that anchors the protein in the membrane as a result the translocated protein ends up as a transmembrane protein inserted in the membrane with a defined orientation in some transmembrane proteins an internal signal sequence is used to start the protein transfer which continues until a stop transfer sequence is reached the two hydrophobic sequences are then released into the bilayer where they remain anchored in complex multipass proteins in which many hydrophobic regions span the bilayer additional pairs of stop and start sequences come into play one sequence reinitiates translocation further down the polypeptide chain and the other stops trans location and causes polypeptide release and so on for subsequent starts and stops thus multipass membrane proteins are stitched into the lipid bilayer as they are being synthesized by a mechanism resembling a sewing machine