Proteins destined for secretion, lysosomes, or the plasma membrane are translated on membrane-bound ribosomes and transferred into the rough ER as their translation proceeds. Ribosomes engaged in the synthesis of secreted proteins are targeted to the ER by signal sequences at the amino terminus of the polypeptide chain. Growing polypeptide chains are then translocated into the ER through protein channels and released into the ER lumen by cleavage of the signal sequence. Integral membrane proteins are inserted into the membrane of the ER by membrane spanning α helices that stop the transfer of the polypeptide chain across the membrane. Polypeptide chains are folded into their correct three dimensional conformations and modified by N-linked glycosylation and addition of GPI anchors within the ER; proteins that are not folded correctly are diverted from the secretory pathway and degraded. The ER is also the major site of lipid synthesis in eukaryotic cells, and smooth ER is abundant in cells that are active in lipid metabolism and detoxification of lipid-soluble drugs.
Proteins are transported from the ER to the cis compartment of the Golgi. Distinct processing events take place as proteins move through the medial and trans compartments to the trans-Golgi network. The N-linked oligosaccharides added to proteins in the ER are modified within the Golgi and proteins destined for lysosomes are specifically phosphorylated on mannose residues. O-linked glycosylation also takes place within the Golgi. In addition, the Golgi apparatus is the site of synthesis of glycolipids, sphingomyelin, and the complex polysaccharides of plant cell walls. Proteins are sorted in the trans-Golgi network for secretion, the plasma membrane, and lysosomes. In polarized cells, proteins are specifically targeted to the apical and basolateral domains of the plasma membrane.
The cytoplasmic surfaces of most vesicles are coated with proteins that drive vesicle budding. The specific molecules to be transported are selected by complexes of small GTP-binding proteins and adaptor proteins that associate with the coat proteins. The initial interaction between vesicles and their target membranes is mediated by the binding of tethering factors to Rab proteins. Subsequent interactions between transmembrane proteins on vesicle and target membranes lead to membrane fusion.
Lysosomes contain acid hydrolases that degrade proteins, nucleic acids, polysaccharides, and lipids. These enzymes function specifically at the acidic pH maintained within lysosomes. Extracellular molecules taken up by endocytosis are transported to endosomes, and late endosomes mature to lysosomes as lysosomal acid hydrolases are delivered from the Golgi. In addition to degradation of extracellular materials, lysosomes are responsible for digestion of the cell's own components by autophagy.