2.2 Traffic in the endoplasmic reticulum and the Golgi network
The ER extends as a network of membranous tubes and sheets throughout the cytoplasm and is the site of synthesis of proteins ultimately destined for the Golgi apparatus, endosomes, lysosomes, the plasma membrane, secretory vesicles and beyond. In animal cells, the Golgi apparatus is usually a single structure located near the nucleus of the cell, consisting of between four and ten flattened cisternae, which are designated the cis, medial or trans Golgi network, depending on their position within the stack. The cis Golgi comprises the cisternae that receive transport vesicles from the ER, and the trans Golgi sorts proteins for onward delivery to the plasma membrane, endosomes, etc. The organisation of the Golgi apparatus depends on the integrity of the microtubule network.
Only proteins that are correctly folded are released from the ER and transported to the cis Golgi where they are further modified and processed. Protein synthesis has numerous quality-control steps of this type, and this extends to protein localisation. Vesicles carrying proteins move between the ER and the cis, medial and trans faces of the Golgi apparatus in both directions (see Figure 16). Primarily, these will be proteins destined for onward delivery to downstream compartments, such as secretory vesicles, but some proteins are required in the Golgi itself and these have the appropriate signal patches to ensure they are retained in this compartment.
However, there is always some degree of error in biological systems, so that proteins intended to function in the ER will occasionally be carried to the Golgi apparatus. A reverse transport system, or ER retrieval pathway, ensures that they are returned to their correct compartment. Signal sequences at the C-terminus of membrane-bound ER proteins and different sequences in soluble ER proteins control their localisation, as described in Section 3.5.
Proteins that are destined for endosomal compartments, the plasma membrane or secretion are carried in vesicles that bud from the trans Golgi. The pH in the ER is neutral, but as proteins move from the cis to the trans Golgi they are exposed to increasingly acidic conditions. The pH affects the activity of the enzymes in the different compartments and may regulate how well proteins bind to sorting receptors in each compartment. Beyond the Golgi, specialised endosomal compartments in some cells have even lower pH values, maintained by proton pumps. One of the key functions of protein sorting is to move molecules to a compartment where they are in an appropriate environment to function, or where they can be stored.