Most proteins and lipids leaving the endoplasmic reticulum are packaged in vesicles or incorporated in tubulo-vesicular compartments that are detached from the endoplasmic reticulum membrane (Figure 1). They are shipped to the Golgi apparatus. There are ribosome-free regions distributed along the endoplasmic reticulum membranes, referred as transition zones, where these vesicles and their cargoes are assembled. Transition zones are about 0,5 µm in length and, at least in mammals cells, are quite stable in both time and space.
Transition zones are associated with the Golgi stacks. They are close to each other. This makes sense because the communication is more efficient. Vesicles don't need to travel long distances and the existence of the Golgi apparatus itself depends on a continuous process of vesicle incoming. It has been observed that a new transition zone led quickly to the nearby formation of a new Golgi stack. On the contrary, if a transition zone disappears, the associated Golgi cisternae are also lost. Transition zones can fuse with others and one transition zone can be split in two. Their associated Golgi stacks match this behavior.
Vesicles budding from the transition zones are COPII coated vesicles (Figure 1). Several proteins are involved in the formation of this COPII molecular framework: Sec16, Sar1 GTPases, Sec23/24 and Sec13/31. In this order, they are assembled at the cytosolic surface of the transition zone membranes. Transition zones are the more suitable environments for the assembling of COPII coats by having a particular membrane lipid composition and a higher concentration of the protein Sec16, which recruit Sec23/24 proteins, that in turn recruit Sec13/36.
COPII proteins participate in two mechanisms: a) vesicle formation and b) selection of cargoes.
a) COPII proteins, mostly the external layer formed by Sec13/31, are involved in the formation of the vesicle. To do this, they induce the bending of the membrane by producing mechanical tensions and folds in the membrane for form the vesicle. Furthermore, COPII proteins are thought to participate in the excision of the vesicle.
b) Two types of cargoes are going to be transported: transmembrane cargo and soluble cargo. Soluble cargoes must be "fished" by transmembrana receptors. The cytosolic domains of both, transmembrane cargoes and receptors, are recognized by COPII proteins and included in the vesicle. The recognition is mediated by Sec 24 proteins. Thus, COPII proteins are needed for selecting molecules to be transported in the vesicle. In addition, any protein to be transported has to be properly folded. Otherwise, it will be removed from the endoplasmic reticulum before the recognition. A quality control of proteins is always at work in the endoplasmic reticulum.
COPII coated vesicles are released from the transition zones of the endoplasmic reticulum, they partially lose the protein coat, and are fused together to form the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) or tubule vesicular transporter, which is moved by microtubules and motor proteins toward the cis face of the Golgi apparatus. All the ERGIC bodies arriving at the cis face are fused to form the cis cisternae of the Golgi apparatus.
COPII coated vesicles is the usual way to travel from the endoplasmic reticulum to the Golgi apparatus. However, there are alternatives, or variations, to this vesicular mechanism. For example, a typical COPII vesicle of about 60-90 nm in size, cannot enclose a pro-collagen molecule, which is 300 to 400 nm long. Likewise, chylomicrons traveling from the reticulum to the Golgi apparatus need larger special vesicles. It looks like that the activity of the Sar1 GTPase is important for modifying the vesicle coat and then produce vesicles larger than 500 nm, where larger molecules can fit.
ERGIC body matures during the way toward the Golgi apparatus. This maturing process brings a progressively change of the molecular composition of its membrane, that in turn allows the attachment of some cytosolic proteins to its membrane. Thus, COPI proteins will be recruited to the ERGIC membrane and will form vesicles with selected cargoes. This is similar process to that of the generation of COPII vesicles in the endoplasmic reticulum, but COPI vesicles will be sent to the endoplasmic reticulum. It is a recycling pathway that will send back resident proteins belonging to the endoplasmic reticulum. Endoplasmic reticulum resident transmembrane proteins will be directly selected by COPI proteins, but soluble resident proteins should be picked up by transmembrane receptors, known as KDEL receptors, which in turn are catched by COPI proteins. All these interactions are mediated by specific amino acid sequences or signal peptides. So, COPI vesicles fuse with the endoplasmic reticulum and release transmembrane proteins in the endoplasmic reticulum membrane by lateral diffusion, whereas soluble proteins are uncoupled from KDEL and set free in the lumen. KDEL, now without any bound ligand, will be included again into COPII vesicles for a new journey, so it is permanently traveling between the endoplasmic reticulum and ERGIC-Golgi compartments. There is an increase in the pH value as we move from the endoplasmic reticulum to the Golgi apparatus, so that ERGIC is more basic that the endoplasmic reticulum. KDEL binds ligands in more basic enviroments, but the affinity for them decreases in more acidic environments, so that ligands are released, which happens in the endoplasmic reticulum. In other words, the differences in pH values between ERGIC-Golgi and endoplasmic reticulum allow fetching ligands by KDEL in the ERGI-Golgi and releasing them in endoplasmic the reticulum.
Antonny B, Schekman R . ER export: public transportation by the COPII coach. 2001. Current opinion in cell biology 13:438-443.