6. Budding and fusion reactions

25.5 An alternative model for protein transport

Are coated vesicles responsible for all transport between membranous systems? There are conflicting models for the nature of forward transport from the ER, through Golgi cisternae, and then from the TGN to the plasma membrane.

The vesicular model for anterograde transport proposes that the Golgi cisternae are fixed structures that gain and lose proteins by the processes of vesicle fusion and budding. The process starts when COP-II coated vesicles bud at the ER and transport cargo to the Golgi. It is not clear whether the vesicles that move between Golgi cisternae would also have COP-II coats. The natures of the coat(s) of vesicles that proceed from the Golgi to the plasma membrane remain unknown (for review see Rothman and Orci, 1992; Rothman, 1994; Rothman, 1996).

An alternative model for anterograde transport suggests that there is cisternal maturation. Instead of being fixed structures, cisternae move from the cis side of the Golgi to the trans side, maturing into more trans-like types of cisternae by changes in their protein constitution. Evidence for cisternal maturation has been provided by following the fate of a substrate protein that is too large to be incorporated into vesicles. Procollagen type I assembles into rod-like triple helices that are ~300 nm long in the lumen of the ER. These rods can be followed as they move into the cis-Golgi and through the Golgi to the TGN. Because they remain intact, and are too large to be incorporated into vesicles (COP-coated vesicles are 60 V90 nm in diameter), this means that the membrane-bound compartment containing the rods must itself have moved from the cis to the trans side of the Golgi. This shows at least the plausibility of cisternal maturation, although it does not demonstrate whether normal cargo proteins are carried by vesicles or also move by cisternal maturation (Bonfanti et al., 1998).

To take the model for cisternal maturation to its extremes, the cis-Golgi could be formed by fusion between COP-II coated vesicles that bud from the ER; this process might also involve larger tubules. The cis-Golgi cisternae would move steadily forward until they mature into the trans-Golgi cisternae. At the TGN, secretory vesicles might form by fragmenting into tubular structures, without requiring any special type of coat. Of course, as cisternae mature, proteins that belong to more cis-like cisternae must be retrieved; this would occur by COP-I-mediated retrograde vesicular transport.

The outstanding question is the relative quantitative importance of cisternal maturation and vesicular transport for the anterograde direction. Whichever model applies, the TGN provides the sorting center for directing proteins on the anterograde route to the plasma membrane, endosomes, or other membrane surfaces (for review see Griffiths and Simons, 1986).

Reviews

Griffiths, G. and Simons, K. (1986). The trans Golgi network: sorting at the exit site of the Golgi complex. Science 234, 438-443.

Rothman, J. E. (1994). Mechanisms of intracellular protein transport. Nature 372, 55-68.

Rothman, J. E. (1996). Protein sorting by transport vesicles. Science 272, 227-234.

Rothman, J. E. and Orci, L. (1992). Molecular dissection of the secretory pathway. Nature 355, 409-415.

Research

Bonfanti, L. et al. (1998). Procollagen traverses the Golgi stack without leaving the lumen of cisternae: evidence for cisternal maturation. Cell 95, 993-1003.