T.J.G. ettema, Biochem. Soc. Trans. 41: 451–457, 2013.)
To understand the general principles by which sorting signals operate, it is important to distinguish three fundamentally different ways by which proteins move from one compartment to another. These three mechanisms are described below, and the transport steps at which they operate are outlined in Figure 12–5. We discuss the first two mechanisms (gated transport and transmembrane transport) in this chapter, and the third (vesicular transport, green arrows in Figure 12–5) in Chapter 13.
1.
In gated transport, proteins and RNA molecules move between the cytosol and the nucleus through nuclear pore complexes in the nuclear envelope. The nuclear pore complexes function as selective gates that support the active transport of specific macromolecules and macromolecular assemblies between the two topologically equivalent spaces, although they also allow free diffusion of smaller molecules.
2.
In protein translocation, transmembrane protein translocators directly transport specific proteins across a membrane from the cytosol into a space that is topologically distinct. The transported protein molecule usually must unfold to snake through the translocator. The initial transport of selected proteins from the cytosol into the ER lumen or mitochondria, for example, occurs in this way. Integral membrane proteins often use the same translocators but translocate only partially across the membrane, so that the protein becomes embedded in the lipid bilayer.
3.
In vesicular transport, membrane-enclosed transport intermediates— which may be small, spherical transport vesicles or larger, irregularly shaped organelle fragments—ferry proteins from one topologically equivalent compartment to another. The transport vesicles and fragments become loaded with a cargo of molecules derived from the lumen of one compartment as they bud and pinch off from its membrane; they discharge their cargo into a second compartment by fusing with the membrane enclosing that compartment (Figure 12–6). The transfer of soluble proteins from the ER to the Golgi apparatus, for example, occurs in this way. Because the
Figure 12–5 A simplified “roadmap” of protein traffic within a eukaryotic cell. proteins can move from one compartment to another by gated transport (red), protein translocation (blue), or vesicular transport (green). The sorting signals that direct a given protein’s movement through the system, and thereby determine its eventual location in the cell, are contained in each protein’s amino acid sequence. The journey begins with the synthesis of a protein on a ribosome in the cytosol and, for many proteins, terminates when the protein reaches its final destination. other proteins shuttle back and forth between the nucleus and cytosol. at each intermediate station (boxes), a decision is made as to whether the protein is to be retained in that compartment or transported further. a sorting signal may direct either retention in or exit from a compartment.
We shall refer to this figure often as a guide in this chapter and the next, highlighting in color the particular pathway being discussed.
Figure 12–4 Topologically equivalent compartments in the secretory and endocytic pathways in a eukaryotic cell. Compartments are said to be topologically equivalent if they can communicate with one another, in the sense that molecules can get from one to the other without having to cross a membrane. Topologically equivalent spaces are shown in red. (a) molecules can be carried from one compartment to another topologically equivalent compartment by vesicles that bud from one and fuse with the other. (B) in principle, cycles of membrane budding and fusion permit the lumen of any of the organelles shown to communicate with any other and with the cell exterior by means of transport vesicles. Blue arrows indicate the extensive outbound and inbound vesicular traffic (discussed in Chapter 13). some organelles, most notably mitochondria and (in plant cells) plastids, do not take part in this communication and are isolated from the vesicular traffic between organelles shown here.
= gated transport = transmembrane transport = vesicular transport KEY:
Figure 12–6 Vesicle budding and fusion during vesicular transport.