Membrane cycling between the ER and Golgi apparatus and its role in biosynthetic transport.

Membrane traffic between the ER and Golgi is now recognized as a carefully regulated process controlled by distinct anterograde (to the Golgi) and retrograde (to the ER) pathways. These pathways link two organelles with different morphologies, structures, and localizations within the cell. The ER, which is involved in multiple cellular functions including protein biosynthesis and folding, extends to the cell periphery and forms a dynamic tubule reticulum. By contrast, the Golgi apparatus, which functions in membrane sorting and recycling events, is localized at the center of the cell near the MTOC and is comprised of compact cisternal units. The required transport into the Golgi apparatus of newly synthesized proteins exported from the ER offers a twofold advantage to the cell. First, the rate of movement of membrane and protein through the biosynthetic pathway can be controlled by the selective use of a recycling pathway. Second, membrane moving through the biosynthetic pathway enters a structure specialized for sorting of membrane to different final destinations in the cell Control of biosynthetic transport within the ER/Golgi system involves the utilization of two alternative transport pathways: anterograde (ER to Golgi) and retrograde (Golgi to ER). These two pathways share a common regulatory system involving membrane assembly/disassembly of cytosolic coatomer proteins. Thus, conditions that favor irreversible coatomer binding (i.e., GTP gamma S) inhibit retrograde transport while producing anterograde transport intermediates. Conditions that prevent coatomer binding (i.e., BFA) inhibit anterograde transport and enhance retrograde transport. The underlying biochemical machinery that normally balances anterograde and retrograde membrane traffic between the ER and Golgi is only just beginning to be understood. Any model to explain this system, however, must account for the morphologic characteristics of the membranes involved. Whereas anterograde traffic involves discontinuous "coated" structures moving from peripheral sites in the ER toward the central Golgi, retrograde traffic utilizes continuous "noncoated" tubule structures that move from a central site (i.e., the CGN) to the peripheral ER (see Figure 3). Such a system maximizes volume transport (utilizing vacuolar structures) in the anterograde direction and membrane transport (utilizing tubules) in the retrograde direction. It is therefore ideal for sorting of bulk flow lumenal contents from recycling membrane early in the biosynthetic pathway.