Chapter 12 Intracellular Compartments and Protein Sorting Biology PDF

641 chapter Intracellular Compartments and Protein Sorting 12 Unlike a bacterium, which generally consists of a single intracellular compart-...

641 chapter Intracellular Compartments and Protein Sorting 12 Unlike a bacterium, which generally consists of a single intracellular compart- In This Chapter ment surrounded by a plasma membrane, a eukaryotic cell is elaborately sub- divided into functionally distinct, membrane-enclosed compartments. Each The Compartmentalization compartment, or organelle, contains its own characteristic set of enzymes and of Cells other specialized molecules, and complex distribution systems transport specific products from one compartment to another. To understand the eukaryotic cell, it THE TRANSPORT OF is essential to know how the cell creates and maintains these compartments, what MOLECULES BETWEEN THE occurs in each of them, and how molecules move between them. NUCLEUS AND THE CYTOSOL Proteins confer upon each compartment its characteristic structural and functional properties. They catalyze the reactions that occur there and selectively THE TRANSPORT OF PROTEINS transport small molecules into and out of the compartment. For membrane-en- INTO MITOCHONDRIA AND closed organelles in the cytoplasm, proteins also serve as organelle-specific sur- CHLOROPLASTS face markers that direct new deliveries of proteins and lipids to the appropriate organelle. PEROXISOMES An animal cell contains about 10 billion (1010) protein molecules of perhaps 10,000 kinds, and the synthesis of almost all of them begins in the cytosol, the THE ENDOPLASMIC RETICULUM space of the cytoplasm outside the membrane-enclosed organelles. Each newly synthesized protein is then delivered specifically to the organelle that requires it. The intracellular transport of proteins is the central theme of both this chapter and the next. By tracing the protein traffic from one compartment to another, one can begin to make sense of the otherwise bewildering maze of intracellular mem- branes. The Compartmentalization of Cells In this brief overview of the compartments of the cell and the relationships between them, we organize the organelles conceptually into a small number of discrete families, discuss how proteins are directed to specific organelles, and explain how proteins cross organelle membranes. All Eukaryotic Cells Have the Same Basic Set of Membrane- enclosed Organelles Many vital biochemical processes take place in membranes or on their surfaces. Membrane-bound enzymes, for example, catalyze lipid metabolism; and oxida- tive phosphorylation and photosynthesis both require a membrane to couple the transport of H+ to the synthesis of ATP. In addition to providing increased mem- brane area to host biochemical reactions, intracellular membrane systems form enclosed compartments that are separate from the cytosol, thus creating function- ally specialized aqueous spaces within the cell. In these spaces, subsets of mol- ecules (proteins, reactants, ions) are concentrated to optimize the biochemical reactions in which they participate. Because the lipid bilayer of cell membranes is impermeable to most hydrophilic molecules, the membrane of an organelle must contain membrane transport proteins to import and export specific metabolites. Each organelle membrane must also have a mechanism for importing, and incor- porating into the organelle, the specific proteins that make the organelle unique. 642 Chapter 12: Intracellular Compartments and Protein Sorting Figure 12–1 The major intracellular endosome compartments of an animal cell. The cytosol (gray), endoplasmic reticulum, Golgi apparatus, nucleus, mitochondrion, mitochondrion lysosome endosome, lysosome, and peroxisome are distinct compartments isolated from the Golgi rest of the cell by at least one selectively apparatus permeable membrane (see Movie 9.2). cytosol peroxisome endoplasmic reticulum with membrane-bound polyribosomes free ribosomes nucleus plasma membrane 15 µm Figure 12–1 illustrates the major intracellular compartments common to eukaryotic cells. The nucleus contains the genome (aside from mitochondrial and chloroplast DNA), and it is the principal site of DNA and RNA synthesis. The sur- rounding cytoplasm consists of the cytosol and the cytoplasmic organelles sus- pended in it. The cytosol constitutes a little more than half the total volume of MBoC6 m12.01/12.01 the cell, and it is the main site of protein synthesis and degradation. It also per- forms most of the cell’s intermediary metabolism—that is, the many reactions that degrade some small molecules and synthesize others to provide the building blocks for macromolecules (discussed in Chapter 2). About half the total area of membrane in a eukaryotic cell encloses the laby- rinthine spaces of the endoplasmic reticulum (ER). The rough ER has many ribo- somes bound to its cytosolic surface. Ribosomes are organelles that are not mem- brane-enclosed; they synthesize both soluble and integral membrane proteins, most of which are destined either for secretion to the cell exterior or for other organelles. We shall see that, whereas proteins are transported into other mem- brane-enclosed organelles only after their synthesis is complete, they are trans- ported into the ER as they are synthesized. This explains why the ER membrane is unique in having ribosomes tethered to it. The ER also produces most of the lipid for the rest of the cell and functions as a store for Ca2+ ions. Regions of the ER that lack bound ribosomes are called smooth ER. The ER sends many of its proteins and lipids to the Golgi apparatus, which often consists of organized stacks of disc- like compartments called Golgi cisternae. The Golgi apparatus receives lipids and proteins from the ER and dispatches them to various destinations, usually cova- lently modifying them en route. Mitochondria and chloroplasts generate most of the ATP that cells use to drive reactions requiring an input of free energy; chloroplasts are a specialized version of plastids (present in plants, algae, and some protozoa), which can also have other functions, such as the storage of food or pigment molecules. Lysosomes con- tain digestive enzymes that degrade defunct intracellular organelles, as well as macromolecules and particles taken in from outside the cell by endocytosis. On the way to lysosomes, endocytosed material must first pass through a series of organelles called endosomes. Finally, peroxisomes are small vesicular compart- ments that contain enzymes used in various oxidative reactions. In general, each membrane-enclosed organelle performs the same set of basic functions in all cell types. But to serve the specialized functions of cells, these organelles vary in abundance and can have additional properties that differ from cell type to cell type. On average, the membrane-enclosed compartments together occupy nearly half the volume of a cell (Table 12–1), and a large amount of intracellular mem- brane is required to make them. In liver and pancreatic cells, for example, the THE COMPARTMENTALIZATION OF CELLS 643 endoplasmic reticulum has a total membrane surface area that is, respectively, Table 12–1 Relative Volumes 25 times and 12 times that of the plasma membrane (Table 12–2). The mem- Occupied by the Major brane-enclosed organelles are packed tightly in the cytoplasm, and, in terms of Intracellular Compartments in a area and mass, the plasma membrane is only a minor membrane in most eukary- Liver Cell (Hepatocyte) otic cells (Figure 12–2). The abundance and shape of membrane-enclosed organelles are regulated to Intracellular Percentage meet the needs of the cell. This is particularly apparent in cells that are highly spe- compartment of total cell volume cialized and therefore disproportionately rely on specific organelles. Plasma cells, for example, which secrete their own weight every day in antibody molecules into Cytosol 54 the bloodstream, contain vastly amplified amounts of rough ER, which is found in large, flat sheets. Cells that specialize in lipid synthesis also expand their ER, Mitochondria 22 but in this case the organelle forms a network of convoluted tubules. Moreover, Rough ER 9 membrane-enclosed organelles are often found in characteristic positions in the cisternae cytoplasm. In most cells, for example, the Golgi apparatus is located close to the nucleus, whereas the network of ER tubules extends from the nucleus throughout Smooth ER 6 cisternae plus the entire cytosol. These characteristic distributions depend on interactions of the Golgi cisternae organelles with the cytoskeleton. The localization of both the ER and the Golgi apparatus, for instance, depends on an intact microtubule array; if the microtu- Nucleus 6 bules are experimentally depolymerized with a drug, the Golgi apparatus frag- Peroxisomes 1 ments and disperses throughout the cell, and the ER network collapses toward the cell center (discussed in Chapter 16). The size, shape, composition, and location Lysosomes 1 are all important and regulated features of these organelles that ultimately con- tribute to the organelle’s function. Endosomes 1 Evolutionary Origins May Help Explain the Topological Relationships of Organelles To understand the relationships between the compartments of the cell, it is help- ful to consider how they might have evolved. The precursors of the first eukaryotic cells are thought to have been relatively simple cells that—like most bacterial and Table 12–2 Relative Amounts of Membrane Types in Two Kinds of Eukaryotic Cells Membrane Type Percentage of total cell membrane Liver hepatocyte* Pancreatic exocrine cell* Plasma membrane 2 5 Rough ER membrane 35 60 Smooth ER membrane 16