The Secretory Pathway From History to the State of the Art - Fusion of Biological Membranes and Related Problems - page 6

However, a wealth of information from biochemical, morphological
and genetic approaches strongly supports the vesicular model as the general
mode of intracellular transport. It may well be that the cisternal matura-
tion model applies to some kind of cargo in specialized cells.
In the following sections, we will focus on the major types of transport
vesicles: (i) COPII-coated vesicles for export from the ER; (ii) COPI-coated
vesicles for transport into and through the Golgi in anterograde direction
as well as transport between the Golgi and the ER in retrograde direction,
and (iii) clathrin-coated vesicles for transport between the TGN and the
plasma membrane (Figure 1).
3.1. Export from the ER
Export from the ER is the first step in the vectorial movement of cargo
through the secretory pathway in eucaryotic cells. Originally, distinct exit
sites in the ER for proteins and lipids have been defined morphologically
in specialized secretory cells (Orci et al ., 1994; Palade, 1975). Specialized
export complexes of the ER have been suggested to exist in all eucaryotic
cells and to consist of small vesicles and tubular structures that may fuse
with one another thus giving rise to the ERGIC. Based on quantitative
immunocytochemistry and an evaluation of cargo, it is believed that vesic-
ular tubular structures represent the sites where sorting and concentration
of cargo destined for ER export occurs (Bannykh et al ., 1996; Balch et al .,
1994; Mizuno and Singer, 1993).
3.1.1. COPII-Coated Vesicles
The generation of transport intermediates from the ER is driven by
the recruitment of a set of soluble proteins from the cytoplasm to the ER
membrane that form a coat structure, termed COPII (Barlowe et al ., 1994,
reviewed in: Barlowe, 1998). Components of the COPII coat have initially
been characterized by use of a collection of Sec (Sec for secretion) mutants
of S. cerevisiae which are defective at distinct steps in intracellular trans-
port (Kaiser and Schekman, 1990). This led to the identification of three
soluble protein components that make up the coat of ER-derived transport
vesicles in yeast: Sar1p, Sec23p complex and Sec13p complex (Table I).
Sar1p is a GTPase that shares primary structure identity with the Ras family
of GTPases (Barlowe et al ., 1993; Nakano and Muramatsu, 1989). The
Sec23p complex migrates at 400 kDa and is composed of two proteins: Sec
23p, an 85 kDa protein, and a tightly associated protein of 105 kDa, called
Sec24p (Hicke et al ., 1992). The Sec 13p complex has a molecular mass of
700kDa and contains the 34kDa Sec13p subunit (Pryer et al ., 1993) and the