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of external signals, including hormones and other ligands, and sites for the recognition and attachment of other cells. Internally, plasma membranes can act as points of attachment for intracellular structures, in particular those concerned with cell motility and other cytoskeletal functions. Cell membranes are synthesized by the rough endoplasmic reticulum in conjunction with the Golgi apparatus. ###### Cell coat (glycocalyx) The external surface of a plasma membrane differs structurally from internal membranes in that it possesses an external, fuzzy, carbohydraterich coat, the glycocalyx. The cell coat forms an integral part of the plasma membrane, projecting as a diffusely filamentous layer 2–20 nm or more from the lipoprotein surface. The cell coat is composed of the carbohydrate portions of glycoproteins and glycolipids embedded in the plasma membrane (see Fig. 1.3). The precise composition of the glycocalyx varies with cell type; many tissue- and cell type-specific antigens are located in the coat, including the major histocompatibility complex of the immune system and, in the case of erythrocytes, blood group antigens. Therefore, the glycocalyx plays a significant role in organ transplant compatibility. The glycocalyx found on apical microvilli of enterocytes, the cells forming the lining epithelium of the intestine, consists of enzymes involved in the digestive process. Intestinal microvilli are cylindrical projections (1–2 µm long and about 0.1 µm in diameter) forming a closely packed layer called the brush border that increases the absorptive function of enterocytes. ###### Cytoplasm ###### Compartments and functional organization The cytoplasm consists of the cytosol, a gel-like material enclosed by the cell or plasma membrane. The cytosol is made up of colloidal proteins such as enzymes, carbohydrates and small protein molecules, together with ribosomes and ribonucleic acids. The cytoplasm contains two cytomembrane systems, the endoplasmic reticulum and Golgi apparatus, as well as membrane-bound organelles (lysosomes, peroxisomes and mitochondria), membrane-free inclusions (lipid droplets, glycogen and pigments) and the cytoskeleton. The nuclear contents, the nucleoplasm, are separated from the cytoplasm by the nuclear envelope. ###### Endoplasmic reticulum The endoplasmic reticulum is a system of interconnecting membranelined channels within the cytoplasm (Fig. 1.4). These channels take various forms, including cisternae (flattened sacs), tubules and vesicles. The membranes divide the cytoplasm into two major compartments. The intramembranous compartment, or cisternal space, is where secretory products are stored or transported to the Golgi complex and cell exterior. The cisternal space is continuous with the perinuclear space. Structurally, the channel system can be divided into rough or granu lar endoplasmic reticulum (RER), which has ribosomes attached to its outer, cytosolic surface, and smooth or agranular endoplasmic reticulum (SER), which lacks ribosomes. The functions of the endoplasmic reticulum vary greatly and include: the synthesis, folding and transport of proteins; synthesis and transport of phospholipids and steroids; and storage of calcium within the cisternal space and regulated release into the cytoplasm. In general, RER is well developed in cells that produce **Fig 1 4 Smooth endoplasmic reticulum with associated vesicles The** abundant proteins; SER is abundant in steroid-producing cells and muscle cells. A variant of the endoplasmic reticulum in muscle cells is the sarcoplasmic reticulum, involved in calcium storage and release for muscle contraction. For further reading on the endoplasmic reticulum, see Bravo et al (2013). ###### Smooth endoplasmic reticulum The smooth endoplasmic reticulum (see Fig. 1.4) is associated with carbohydrate metabolism and many other metabolic processes, including detoxification and synthesis of lipids, cholesterol and steroids. The membranes of the smooth endoplasmic reticulum serve as surfaces for the attachment of many enzyme systems, e.g. the enzyme cytochrome P450, which is involved in important detoxification mechanisms and is thus accessible to its substrates, which are generally lipophilic. The membranes also cooperate with the rough endoplasmic reticulum and the Golgi apparatus to synthesize new membranes; the protein, carbohydrate and lipid components are added in different structural compartments. The smooth endoplasmic reticulum in hepatocytes contains the enzyme glucose-6-phosphatase, which converts glucose-6phosphate to glucose, a step in gluconeogenesis. ###### Rough endoplasmic reticulum The rough endoplasmic reticulum is a site of protein synthesis; its cytosolic surface is studded with ribosomes (Fig. 1.5E). Ribosomes only bind to the endoplasmic reticulum when proteins targeted for secretion begin to be synthesized. Most proteins pass through its membranes and accumulate within its cisternae, although some integral membrane proteins, e.g. plasma membrane receptors, are inserted into the rough endoplasmic reticulum membrane, where they remain. After passage from the rough endoplasmic reticulum, proteins remain in membranebound cytoplasmic organelles such as lysosomes, become incorporated into new plasma membrane, or are secreted by the cell. Some carbohydrates are also synthesized by enzymes within the cavities of the rough endoplasmic reticulum and may be attached to newly formed protein (glycosylation). Vesicles are budded off from the rough endoplasmic reticulum for transport to the Golgi as part of the protein-targeting mechanism of the cell. ###### Ribosomes, polyribosomes and protein synthesis Ribosomes are macromolecular machines that catalyse the synthesis of proteins from amino acids; synthesis and assembly into subunits takes place in the nucleolus and includes the association of ribosomal RNA (rRNA) with ribosomal proteins translocated from their site of synthesis in the cytoplasm. The individual subunits are then transported into the cytoplasm, where they remain separate from each other when not actively synthesizing proteins. Ribosomes are granules approximately 25 nm in diameter, composed of rRNA molecules and proteins assembled into two unequal subunits. The subunits can be separated by their sedimentation coefficients (S) in an ultracentrifuge into larger 60S and smaller 40S components. These are associated with 73 different proteins (40 in the large subunit and 33 in the small), which have structural and enzymatic functions. Three small, highly convoluted rRNA strands (28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is in the small subunit. A typical cell contains millions of ribosomes. They may form groups (polyribosomes or polysomes) attached to messenger RNA (mRNA), which they translate during protein synthesis for use outside the system of membrane compartments, e.g. enzymes of the cytosol and cytoskeletal proteins. Some of the cytosolic products include proteins that can be inserted directly into (or through) membranes of selected organelles, such as mitochondria and peroxisomes. Ribosomes may be attached to the membranes of the rough endoplasmic reticulum (see Fig. 1.5E). In a mature polyribosome, all the attachment sites of the mRNA are occupied as ribosomes move along it, synthesizing protein according to its nucleotide sequence. Consequently, the number and spacing of ribosomes in a polyribosome indicate the length of the mRNA molecule and hence the size of the protein being made. The two subunits have separate roles in protein synthesis. The 40S subunit is the site of attachment and translation of mRNA. The 60S subunit is responsible for the release of the new protein and, where appropriate, attachment to the endoplasmic reticulum via an intermediate docking protein that directs the newly synthesized protein through the membrane into the cisternal space. ###### Golgi apparatus (Golgi complex) The Golgi apparatus is a distinct cytomembrane system located near the -----
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###### CHAPTER Basic structure and function of cells ##### 1 ###### CELL STRUCTURE ###### GENERAL CHARACTERISTICS OF CELLS The shapes of mammalian cells vary widely depending on their interactions with each other, their extracellular environment and internal structures. Their surfaces are often highly folded when absorptive or transport functions take place across their boundaries. Cell size is limited by rates of diffusion, either that of material entering or leaving cells, or that of diffusion within them. Movement of macromolecules can be much accelerated and also directed by processes of active transport across the plasma membrane and by transport mechanisms within the cell. According to the location of absorptive or transport functions, apical microvilli (Fig. 1.1) or basolateral infoldings create a large surface area for transport or diffusion. Motility is a characteristic of most cells, in the form of movements of cytoplasm or specific organelles from one part of the cell to another. It also includes: the extension of parts of the cell surface such as pseudopodia, lamellipodia, filopodia and microvilli; locomotion of entire cells, as in the amoeboid migration of tissue macrophages; the beating of flagella or cilia to move the cell (e.g. in spermatozoa) or fluids overlying it (e.g. in respiratory epithelium); cell division; and muscle contraction. Cell movements are also involved in the uptake of materials from their environment (endocytosis, phagocytosis) and the passage of large molecular complexes out of cells (exocytosis, secretion). Epithelial cells rarely operate independently of each other and com monly form aggregates by adhesion, often assisted by specialized intercellular junctions. They may also communicate with each other either by generating and detecting molecular signals that diffuse across intercellular spaces, or more rapidly by generating interactions between membrane-bound signalling molecules. Cohesive groups of cells constitute tissues, and more complex assemblies of tissues form functional systems or organs. Most cells are between 5 and 50 µm in diameter: e.g. resting lym phocytes are 6 µm across, red blood cells 7.5 µm and columnar epithelial cells 20 µm tall and 10 µm wide (all measurements are approximate). Some cells are much larger than this: e.g. megakaryocytes of the bone marrow and osteoclasts of the remodelling bone are more than 200 µm in diameter. Neurones and skeletal muscle cells have relatively extended shapes, some of the former being over 1 m in length. ###### CELLULAR ORGANIZATION Each cell is contained within its limiting plasma membrane, which encloses the cytoplasm. All cells, except mature red blood cells, also contain a nucleus that is surrounded by a nuclear membrane or envelope (see Fig. 1.1; **Fig. 1.2). The nucleus includes: the genome of the** cell contained within the chromosomes; the nucleolus; and other subnuclear structures. The cytoplasm contains cytomembranes and several membrane-bound structures, called organelles, which form separate Mitochondrion Surface projections (cilia, microvilli) Surface invagination Actin filaments Vesicle Cell junctions Desmosome Plasma membrane Peroxisomes Cytosol Nuclear pore Intermediate filaments Smooth endoplasmic reticulum Nuclear envelope Nucleus Rough endoplasmic reticulum Golgi apparatus Nucleolus Ribosome Microtubules Centriole pair Lysosomes Cell surface folds -----
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Combinations of biochemical, biophysical and biological tech niques have revealed that lipids are not homogenously distributed in membranes, but that some are organized into microdomains in the bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in sphingomyelin and cholesterol. The ability of select subsets of proteins to partition into different lipid microdomains has profound effects on their function, e.g. in T-cell receptor and cell–cell signalling. The highly organized environment of the domains provides a signalling, trafficking and membrane fusion environment. -----
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The glycocalyx plays a significant role in maintenance of the integrity of tissues and in a wide range of dynamic cellular processes, e.g. serving as a vascular permeability barrier and transducing fluid shear stress to the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of the glycocalyx on the endothelial surface of large blood vessels precedes inflammation, a conditioning factor of atheromatosis (e.g. deposits of cholesterol in the vascular wall leading to partial or complete obstruction of the vascular lumen). Protein synthesis on ribosomes may be suppressed by a class of RNA molecules known as small interfering RNA (siRNA) or silencing RNA. These molecules are typically 20–25 nucleotides in length and bind (as a complex with proteins) to specific mRNA molecules via their complementary sequence. This triggers the enzymatic destruction of the mRNA or prevents the movement of ribosomes along it. Synthesis of the encoded protein is thus prevented. Their normal function may have antiviral or other protective effects; there is also potential for developing artificial siRNAs as a therapeutic tool for silencing disease-related genes. -----
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External (extracellular) surface Internal (intracellular) surface CC MVMV APMAPM AJCAJC MM MM CyCy LPMLPM NN ENEN **Fig. 1.2 The structural organization and some principal organelles of a** typical cell. This example is a ciliated columnar epithelial cell from human nasal mucosa. The central cell, which occupies most of the field of view, is closely apposed to its neighbours along their lateral plasma membranes. Within the apical junctional complex, these membranes form a tightly sealed zone (tight junction) that isolates underlying tissues from, in this instance, the nasal cavity. Abbreviations: AJC, apical junctional complex; APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN, euchromatic nucleus; LPM, lateral plasma membrane; M, mitochondria; MV, microvilli; N, nucleolus. (Courtesy of Dr Bart Wagner, Histopathology Department, Sheffield Teaching Hospitals, UK.) and distinct compartments within the cytoplasm. Cytomembranes include the rough and smooth endoplasmic reticulum and Golgi apparatus, as well as vesicles derived from them. Organelles include lysosomes, peroxisomes and mitochondria. The nucleus and mitochondria are enclosed by a double-membrane system; lysosomes and peroxisomes have a single bounding membrane. There are also nonmembranous structures, called inclusions, which lie free in the cytosolic compartment. They include lipid droplets, glycogen aggregates and pigments (e.g. lipofuscin). In addition, ribosomes and several filamentous protein networks, known collectively as the cytoskeleton, are found in the cytosol. The cytoskeleton determines general cell shape and supports specialized extensions of the cell surface (microvilli, cilia, flagella). It is involved in the assembly of specific structures (e.g. centrioles) and controls cargo transport in the cytoplasm. The cytosol contains many soluble proteins, ions and metabolites. ###### Plasma membrane Cells are enclosed by a distinct plasma membrane, which shares features with the cytomembrane system that compartmentalizes the cytoplasm and surrounds the nucleus. All membranes are composed of lipids (mainly phospholipids, cholesterol and glycolipids) and proteins, in approximately equal ratios. Plasma membrane lipids form a lipid bilayer, a layer two molecules thick. The hydrophobic ends of each lipid molecule face the interior of the membrane and the hydrophilic ends face outwards. Most proteins are embedded within, or float in, the lipid bilayer as a fluid mosaic. Some proteins, because of extensive hydrophobic regions of their polypeptide chains, span the entire width of the membrane (transmembrane proteins), whereas others are only superficially attached to the bilayer by lipid groups. Both are integral (intrinsic) membrane proteins as distinct from peripheral (extrinsic) **Fig. 1.3 The molecular organization of the plasma membrane, according** to the fluid mosaic model of membrane structure. Intrinsic or integral membrane proteins include diffusion or transport channel complexes, receptor proteins and adhesion molecules. These may span the thickness of the membrane (transmembrane proteins) and can have both extracellular and cytoplasmic domains. Transmembrane proteins have hydrophobic zones, which cross the phospholipid bilayer and allow the protein to ‘float’ in the plane of the membrane. Some proteins are restricted in their freedom of movement where their cytoplasmic domains are tethered to the cytoskeleton. charides and polysaccharides are bound either to proteins (glycoproteins) or to lipids (glycolipids), and project mainly into the extracellular domain (Fig. 1.3). In the electron microscope, membranes fixed and contrasted by heavy metals such as osmium tetroxide appear in section as two densely stained layers separated by an electron-translucent zone – the classic unit membrane. The total thickness of each layer is about 7.5 nm. The overall thickness of the plasma membrane is typically 15 nm. Freezefracture cleavage planes usually pass along the hydrophobic portion of the bilayer, where the hydrophobic tails of phospholipids meet, and split the bilayer into two leaflets. Each cleaved leaflet has a surface and a face. The surface of each leaflet faces either the extracellular surface (ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The extracellular face (EF) and protoplasmic face (PF) of each leaflet are artificially produced during membrane splitting. This technique has also demonstrated intramembranous particles embedded in the lipid bilayer; in most cases, these represent large transmembrane protein molecules or complexes of proteins. Intramembranous particles are distributed asymmetrically between the two half-layers, usually adhering more to one half of the bilayer than to the other. In plasma membranes, the intracellular leaflet carries most particles, seen on its face (the PF). Where they have been identified, clusters of particles usually represent channels for the transmembrane passage of ions or molecules between adjacent cells (gap junctions). Biophysical measurements show the lipid bilayer to be highly fluid, allowing diffusion in the plane of the membrane. Thus proteins are able to move freely in such planes unless anchored from within the cell. Membranes in general, and the plasma membrane in particular, form boundaries selectively limiting diffusion and creating physiologically distinct compartments. Lipid bilayers are impermeable to hydrophilic solutes and ions, and so membranes actively control the passage of ions and small organic molecules such as nutrients, through the activity of membrane transport proteins. However, lipid-soluble substances can pass directly through the membrane so that, for example, steroid hormones enter the cytoplasm freely. Their receptor proteins are either cytosolic or nuclear, rather than being located on the cell surface. Plasma membranes are able to generate electrochemical gradients and potential differences by selective ion transport and actively take up -----
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Cell structure 5 1 RETPaHC CC MMVV AAPPMM AAJJCC Receptor Transmembrane protein pore complex of proteins Carbohydrate residues External (extracellular) surface MM MM CCyy LLPPMM Internal (intracellular) surface NN Lipid bilayer appearance in electron microscope Intrinsic membrane protein Extrinsic Transmembrane protein protein Transport Non-polar tail or diffusion of phospholipid channel Cytoskeletal Polar end of element EENN phospholipid Fig . 1 .3 The molecular organization of the plasma membrane, according to the fluid mosaic model of membrane structure . Intrinsic or integral membrane proteins include diffusion or transport channel complexes, receptor proteins and adhesion molecules . These may span the thickness of the membrane (transmembrane proteins) and can have both extracellular and cytoplasmic domains . Transmembrane proteins have hydrophobic zones, which cross the phospholipid bilayer and allow the Fig . 1 .2 The structural organization and some principal organelles of a protein to ‘float’ in the plane of the membrane . Some proteins are typical cell . This example is a ciliated columnar epithelial cell from human restricted in their freedom of movement where their cytoplasmic domains nasal mucosa . The central cell, which occupies most of the field of are tethered to the cytoskeleton . view, is closely apposed to its neighbours along their lateral plasma membranes . Within the apical junctional complex, these membranes form a tightly sealed zone (tight junction) that isolates underlying tissues from, charides and polysaccharides are bound either to proteins (glycopro- in this instance, the nasal cavity . Abbreviations: AJC, apical junctional teins) or to lipids (glycolipids), and project mainly into the extracellular complex; APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN, domain (Fig. 1.3). euchromatic nucleus; LPM, lateral plasma membrane; M, mitochondria; In the electron microscope, membranes fixed and contrasted by MV, microvilli; N, nucleolus . (Courtesy of Dr Bart Wagner, Histopathology heavy metals such as osmium tetroxide appear in section as two densely Department, Sheffield Teaching Hospitals, UK .) stained layers separated by an electron-translucent zone – the classic unit membrane. The total thickness of each layer is about 7.5 nm. The and distinct compartments within the cytoplasm. Cytomembranes overall thickness of the plasma membrane is typically 15 nm. Freeze- include the rough and smooth endoplasmic reticulum and Golgi appa- fracture cleavage planes usually pass along the hydrophobic portion of ratus, as well as vesicles derived from them. Organelles include lyso- the bilayer, where the hydrophobic tails of phospholipids meet, and somes, peroxisomes and mitochondria. The nucleus and mitochondria split the bilayer into two leaflets. Each cleaved leaflet has a surface and are enclosed by a double-membrane system; lysosomes and peroxi- a face. The surface of each leaflet faces either the extracellular surface somes have a single bounding membrane. There are also non- (ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The membranous structures, called inclusions, which lie free in the cytosolic extracellular face (EF) and protoplasmic face (PF) of each leaflet are compartment. They include lipid droplets, glycogen aggregates and pig- artificially produced during membrane splitting. This technique has ments (e.g. lipofuscin). In addition, ribosomes and several filamentous also demonstrated intramembranous particles embedded in the lipid protein networks, known collectively as the cytoskeleton, are found in bilayer; in most cases, these represent large transmembrane protein the cytosol. The cytoskeleton determines general cell shape and sup- molecules or complexes of proteins. Intramembranous particles are ports specialized extensions of the cell surface (microvilli, cilia, flag- distributed asymmetrically between the two half-layers, usually adher- ella). It is involved in the assembly of specific structures (e.g. centrioles) ing more to one half of the bilayer than to the other. In plasma mem- and controls cargo transport in the cytoplasm. The cytosol contains branes, the intracellular leaflet carries most particles, seen on its face many soluble proteins, ions and metabolites. (the PF). Where they have been identified, clusters of particles usually represent channels for the transmembrane passage of ions or molecules Plasma membrane between adjacent cells (gap junctions). Biophysical measurements show the lipid bilayer to be highly fluid, Cells are enclosed by a distinct plasma membrane, which shares fea- allowing diffusion in the plane of the membrane. Thus proteins are able tures with the cytomembrane system that compartmentalizes the cyto- to move freely in such planes unless anchored from within the cell. plasm and surrounds the nucleus. All membranes are composed of Membranes in general, and the plasma membrane in particular, form lipids (mainly phospholipids, cholesterol and glycolipids) and pro- boundaries selectively limiting diffusion and creating physiologically teins, in approximately equal ratios. Plasma membrane lipids form a distinct compartments. Lipid bilayers are impermeable to hydrophilic lipid bilayer, a layer two molecules thick. The hydrophobic ends of each solutes and ions, and so membranes actively control the passage of ions lipid molecule face the interior of the membrane and the hydrophilic and small organic molecules such as nutrients, through the activity of ends face outwards. Most proteins are embedded within, or float in, the membrane transport proteins. However, lipid-soluble substances can lipid bilayer as a fluid mosaic. Some proteins, because of extensive pass directly through the membrane so that, for example, steroid hor- hydrophobic regions of their polypeptide chains, span the entire width mones enter the cytoplasm freely. Their receptor proteins are either of the membrane (transmembrane proteins), whereas others are only cytosolic or nuclear, rather than being located on the cell surface. superficially attached to the bilayer by lipid groups. Both are integral Plasma membranes are able to generate electrochemical gradients (intrinsic) membrane proteins, as distinct from peripheral (extrinsic) and potential differences by selective ion transport, and actively take up membrane proteins, which are membrane-bound only through their or export small molecules by energy-dependent processes. They also association with other proteins. Carbohydrates in the form of oligosac- provide surfaces for the attachment of enzymes, sites for the receptors
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Basic structure and function of cells 5.e1 1 RETPaHC Combinations of biochemical, biophysical and biological tech- niques have revealed that lipids are not homogenously distributed in membranes, but that some are organized into microdomains in the bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in sphingomyelin and cholesterol. The ability of select subsets of proteins to partition into different lipid microdomains has profound effects on their function, e.g. in T-cell receptor and cell–cell signalling. The highly organized environment of the domains provides a signalling, trafficking and membrane fusion environment.
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Basic structure and function of cells 6.e1 1 RETPaHC The glycocalyx plays a significant role in maintenance of the integrity of tissues and in a wide range of dynamic cellular processes, e.g. serving as a vascular permeability barrier and transducing fluid shear stress to the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of the glycocalyx on the endothelial surface of large blood vessels precedes inflammation, a conditioning factor of atheromatosis (e.g. deposits of cholesterol in the vascular wall leading to partial or complete obstruc- tion of the vascular lumen). Protein synthesis on ribosomes may be suppressed by a class of RNA molecules known as small interfering RNA (siRNA) or silencing RNA. These molecules are typically 20–25 nucleotides in length and bind (as a complex with proteins) to specific mRNA molecules via their comple- mentary sequence. This triggers the enzymatic destruction of the mRNA or prevents the movement of ribosomes along it. Synthesis of the encoded protein is thus prevented. Their normal function may have antiviral or other protective effects; there is also potential for developing artificial siRNAs as a therapeutic tool for silencing disease-related genes.
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Gray's Anatomy
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4 1 NOITCES CHAPTER 1 Basic structure and function of cells Epithelial cells rarely operate independently of each other and com- CELL STRUCTURE monly form aggregates by adhesion, often assisted by specialized inter- cellular junctions. They may also communicate with each other either GENERAL CHARACTERISTICS OF CELLS by generating and detecting molecular signals that diffuse across inter- cellular spaces, or more rapidly by generating interactions between The shapes of mammalian cells vary widely depending on their interac- membrane-bound signalling molecules. Cohesive groups of cells con- tions with each other, their extracellular environment and internal stitute tissues, and more complex assemblies of tissues form functional structures. Their surfaces are often highly folded when absorptive or systems or organs. transport functions take place across their boundaries. Cell size is Most cells are between 5 and 50 µm in diameter: e.g. resting lym- limited by rates of diffusion, either that of material entering or leaving phocytes are 6 µm across, red blood cells 7.5 µm and columnar epithe- cells, or that of diffusion within them. Movement of macromolecules lial cells 20 µm tall and 10 µm wide (all measurements are approximate). can be much accelerated and also directed by processes of active trans- Some cells are much larger than this: e.g. megakaryocytes of the bone port across the plasma membrane and by transport mechanisms within marrow and osteoclasts of the remodelling bone are more than 200 µm the cell. According to the location of absorptive or transport functions, in diameter. Neurones and skeletal muscle cells have relatively extended apical microvilli (Fig. 1.1) or basolateral infoldings create a large shapes, some of the former being over 1 m in length. surface area for transport or diffusion. Motility is a characteristic of most cells, in the form of movements of cytoplasm or specific organelles from one part of the cell to another. CELLULAR ORGANIZATION It also includes: the extension of parts of the cell surface such as pseu- dopodia, lamellipodia, filopodia and microvilli; locomotion of entire Each cell is contained within its limiting plasma membrane, which cells, as in the amoeboid migration of tissue macrophages; the beating encloses the cytoplasm. All cells, except mature red blood cells, also of flagella or cilia to move the cell (e.g. in spermatozoa) or fluids overly- contain a nucleus that is surrounded by a nuclear membrane or enve- ing it (e.g. in respiratory epithelium); cell division; and muscle contrac- lope (see Fig. 1.1; Fig. 1.2). The nucleus includes: the genome of the tion. Cell movements are also involved in the uptake of materials from cell contained within the chromosomes; the nucleolus; and other sub- their environment (endocytosis, phagocytosis) and the passage of large nuclear structures. The cytoplasm contains cytomembranes and several molecular complexes out of cells (exocytosis, secretion). membrane-bound structures, called organelles, which form separate Surface projections (cilia, microvilli) Surface invagination Actin filaments Vesicle Mitochondrion Cell junctions Plasma membrane Desmosome Peroxisomes Cytosol Nuclear pore Intermediate filaments Nuclear envelope Smooth endoplasmic Nucleus reticulum Nucleolus Ribosome Rough endoplasmic reticulum Microtubules Golgi apparatus Centriole pair Lysosomes Cell surface folds Fig . 1 .1 The main structural components and internal organization of a generalized cell .
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BaSIC STRuCTuRE aNd fuNCTION Of CEllS 6 1 NOITCES of external signals, including hormones and other ligands, and sites for abundant proteins; SER is abundant in steroid-producing cells and the recognition and attachment of other cells. Internally, plasma mem- muscle cells. A variant of the endoplasmic reticulum in muscle cells is branes can act as points of attachment for intracellular structures, in the sarcoplasmic reticulum, involved in calcium storage and release for particular those concerned with cell motility and other cytoskeletal muscle contraction. For further reading on the endoplasmic reticulum, functions. Cell membranes are synthesized by the rough endoplasmic see Bravo et al (2013). reticulum in conjunction with the Golgi apparatus. Smooth endoplasmic reticulum Cell coat (glycocalyx) The smooth endoplasmic reticulum (see Fig. 1.4) is associated with The external surface of a plasma membrane differs structurally from carbohydrate metabolism and many other metabolic processes, includ- internal membranes in that it possesses an external, fuzzy, carbohydrate- ing detoxification and synthesis of lipids, cholesterol and steroids. The rich coat, the glycocalyx. The cell coat forms an integral part of the membranes of the smooth endoplasmic reticulum serve as surfaces for plasma membrane, projecting as a diffusely filamentous layer 2–20 nm the attachment of many enzyme systems, e.g. the enzyme cytochrome or more from the lipoprotein surface. The cell coat is composed of the P450, which is involved in important detoxification mechanisms and carbohydrate portions of glycoproteins and glycolipids embedded in is thus accessible to its substrates, which are generally lipophilic. The the plasma membrane (see Fig. 1.3). membranes also cooperate with the rough endoplasmic reticulum The precise composition of the glycocalyx varies with cell type; many and the Golgi apparatus to synthesize new membranes; the protein, tissue- and cell type-specific antigens are located in the coat, including carbohydrate and lipid components are added in different structural the major histocompatibility complex of the immune system and, in compartments. The smooth endoplasmic reticulum in hepatocytes con- the case of erythrocytes, blood group antigens. Therefore, the glycocalyx tains the enzyme glucose-6-phosphatase, which converts glucose-6- plays a significant role in organ transplant compatibility. The glycocalyx phosphate to glucose, a step in gluconeogenesis. found on apical microvilli of enterocytes, the cells forming the lining epithelium of the intestine, consists of enzymes involved in the diges- Rough endoplasmic reticulum tive process. Intestinal microvilli are cylindrical projections (1–2 µm The rough endoplasmic reticulum is a site of protein synthesis; its long and about 0.1 µm in diameter) forming a closely packed layer cytosolic surface is studded with ribosomes (Fig. 1.5E). Ribosomes only called the brush border that increases the absorptive function of bind to the endoplasmic reticulum when proteins targeted for secretion enterocytes. begin to be synthesized. Most proteins pass through its membranes and accumulate within its cisternae, although some integral membrane pro- Cytoplasm teins, e.g. plasma membrane receptors, are inserted into the rough endoplasmic reticulum membrane, where they remain. After passage Compartments and functional organization from the rough endoplasmic reticulum, proteins remain in membrane- bound cytoplasmic organelles such as lysosomes, become incorporated The cytoplasm consists of the cytosol, a gel-like material enclosed by into new plasma membrane, or are secreted by the cell. Some carbohy- the cell or plasma membrane. The cytosol is made up of colloidal pro- drates are also synthesized by enzymes within the cavities of the rough teins such as enzymes, carbohydrates and small protein molecules, endoplasmic reticulum and may be attached to newly formed protein together with ribosomes and ribonucleic acids. The cytoplasm contains (glycosylation). Vesicles are budded off from the rough endoplasmic two cytomembrane systems, the endoplasmic reticulum and Golgi reticulum for transport to the Golgi as part of the protein-targeting apparatus, as well as membrane-bound organelles (lysosomes, peroxi- mechanism of the cell. somes and mitochondria), membrane-free inclusions (lipid droplets, glycogen and pigments) and the cytoskeleton. The nuclear contents, Ribosomes, polyribosomes the nucleoplasm, are separated from the cytoplasm by the nuclear and protein synthesis envelope. Ribosomes are macromolecular machines that catalyse the synthesis of Endoplasmic reticulum proteins from amino acids; synthesis and assembly into subunits takes The endoplasmic reticulum is a system of interconnecting membrane- place in the nucleolus and includes the association of ribosomal RNA lined channels within the cytoplasm (Fig. 1.4). These channels take (rRNA) with ribosomal proteins translocated from their site of synthesis various forms, including cisternae (flattened sacs), tubules and vesicles. in the cytoplasm. The individual subunits are then transported into the The membranes divide the cytoplasm into two major compartments. cytoplasm, where they remain separate from each other when not The intramembranous compartment, or cisternal space, is where secre- actively synthesizing proteins. Ribosomes are granules approximately tory products are stored or transported to the Golgi complex and cell 25 nm in diameter, composed of rRNA molecules and proteins assem- exterior. The cisternal space is continuous with the perinuclear space. bled into two unequal subunits. The subunits can be separated by their Structurally, the channel system can be divided into rough or granu- sedimentation coefficients (S) in an ultracentrifuge into larger 60S and lar endoplasmic reticulum (RER), which has ribosomes attached to its smaller 40S components. These are associated with 73 different pro- outer, cytosolic surface, and smooth or agranular endoplasmic reticu- teins (40 in the large subunit and 33 in the small), which have structural lum (SER), which lacks ribosomes. The functions of the endoplasmic and enzymatic functions. Three small, highly convoluted rRNA strands reticulum vary greatly and include: the synthesis, folding and transport (28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is of proteins; synthesis and transport of phospholipids and steroids; and in the small subunit. storage of calcium within the cisternal space and regulated release into A typical cell contains millions of ribosomes. They may form groups the cytoplasm. In general, RER is well developed in cells that produce (polyribosomes or polysomes) attached to messenger RNA (mRNA), which they translate during protein synthesis for use outside the system of membrane compartments, e.g. enzymes of the cytosol and cytoskel- etal proteins. Some of the cytosolic products include proteins that can be inserted directly into (or through) membranes of selected organelles, such as mitochondria and peroxisomes. Ribosomes may be attached to the membranes of the rough endoplasmic reticulum (see Fig. 1.5E). In a mature polyribosome, all the attachment sites of the mRNA are occupied as ribosomes move along it, synthesizing protein according to its nucleotide sequence. Consequently, the number and spacing of ribosomes in a polyribosome indicate the length of the mRNA mole- cule and hence the size of the protein being made. The two subunits have separate roles in protein synthesis. The 40S subunit is the site of attachment and translation of mRNA. The 60S subunit is responsible for the release of the new protein and, where appropriate, attachment to the endoplasmic reticulum via an intermediate docking protein that directs the newly synthesized protein through the membrane into the cisternal space. Golgi apparatus (Golgi complex) Fig . 1 .4 Smooth endoplasmic reticulum with associated vesicles . The The Golgi apparatus is a distinct cytomembrane system located near the dense particles are glycogen granules . (Courtesy of Rose Watson, Cancer nucleus and the centrosome. It is particularly prominent in secretory Research UK .) cells and can be visualized when stained with silver or other metallic
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Gray's Anatomy
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