The Golgi complex comprises a stack of flattened, membrane-bound cisternae that is highly dependent on microtubules for structural integrity. The stack of cisternae can be subdivided into three parts referred to as cis, medial, and trans, with the cis and trans sides facing the ER and the plasma membrane, respectively. Both the cis and trans faces are associated with tubulovesicular bundles of membranes. The ERGIC comprises the bundle on the cis side of the Golgi stack and is the site where incoming proteins from the ER are sorted into those directed for anterograde or for retrograde transport. The tubulovesicular bundle at the trans side is the trans-Golgi network (TGN).
A major feature of the Golgi is polarity. The processing events are temporally and spatially ordered because the processing enzymes have a characteristic distribution across the Golgi stack. In the Golgi, different types of modifications take place (e.g., proteolytic processing, protein O-glycosylation and elaboration of N-linked chains, phosphorylation or sulfation of oligosaccharides, and sulfation of tyro sines as described later). The importance of protein glycosylation for human biology is underlined by the identification of many inherited human disorders that are caused by defects in these processes and cause clinical manifestations as described in Box 1.
Box1. Human Glycosylation Disorders
Extensive analysis has failed to reveal a clear retention motif enabling subdomain-specific retention of resident Golgi proteins. Two possible models have been proposed. One model is retention by preferential interaction with membranes of optimal thickness. It is based on the finding that the transmembrane domains of Golgi proteins are shorter than transmembrane domains of plasma membrane proteins. These differences should allow a preferential interaction with the Golgi membrane lipid bilayer that is thinner than that of plasma membrane. The other model is kin-recognition/oligomerization. It postulates that proteins of a given subdomain of the Golgi membrane can aggregate into large detergent-insoluble oligomers as a way of minimizing lipid-protein contact. This would prevent the entry of proteins into the vesicles and thus their traffic to more distal cisternae. There is evidence in support of both models.
Cargo proteins exit the ER in COPII-coated vesicles that enter the ERGIC and are ultimately delivered to the cis-Golgi either in vesicles or along extended tubules. However, the mechanism whereby cargo proteins move across the Golgi complex from cis to trans remains controversial. Two models have been proposed. The vesicular transport model contends that anterograde transport occurs in vesicles or tubules that traffic cargo in an anterograde direction. The second suggests that there is a cisternal progression and maturation. This alternative model proposes that Golgi cisternae are not fixed structures but move forward from the cis side to the trans side generating an anterograde movement. As cisternae mature, resident Golgi proteins that belong to more cis-like cisternae must be selectively pinched off in vesicles and trafficked back to the cis side of the Golgi stack. This would occur by COPI-mediated retrograde vesicular transport. Although which of these models is correct is currently unclear, a majority of the experimental data support the cisternal maturation model. In particular, technical progress in live-cell imaging provided evidence supporting a very dynamic nature of this organelle as expected by the progression/ maturation model.
The TGN is an important site of intracellular sorting, where proteins bound for lysosomes or regulated secretory vesicles are separated from those entering the constitutive pathway leading to the plasma membrane. The secretion process is called exocytosis. The molecular basis for diversion of proteins into lysosomes and regulated secretory granules are described later.
