INcLuSIoNS
inclusions are nonliving elements of the cell that are freely present within the cytosol and are not mem- brane bound. the major inclusions are glycogen, lipids, pigments, and crystals.
• Glycogen is usually stored in the cytosol in the form of rosettes of β particles that are located in the vicinity of seR elements. these particles are used as an energy deposit that undergoes glyco- genolysis to form glucose, which is converted to pyruvate for use in the citric acid cycle.
• Lipids are stored triglycerides that are catabolized into fatty acids that are fed into the citric acid cycle for the formation of pyruvate. lipids are much more efficient storage forms of energy than glycogen because 1 g of lipid provides twice the amount of AtP as does 1 g of glycogen.
• Usually, pigments are not active metabolically, but may serve protective functions, such as melanin of the skin, which absorbs ultraviolet radiation and serves to protect DnA of epidermal cells from chromosomal damage. Melanin also assists the retina in its function of sight. Another pigment, lipofuscin, is probably formed from fusion of numerous residual bodies, the
membrane bound structures that are undigestible remnants of lysosomal activity.
• Crystals are not usually present in mammalian cells, although sertoli cells of the testis frequently contain crystals of Charcot-Bottscher, whose function, if any, is not understood.
cyToSKELEToN
the cytoskeleton, the three-dimensional structural framework of the cell, is composed of microtubules, thin filaments, and intermediate filaments. this framework not only functions in maintaining the morphologic integrity of the cell, but also permits cells to adhere to one another and to move along connective tissue elements, and facilitates exocytosis, endocytosis, and membrane trafficking within the cytosol. the cytoskeleton assists in the creation of compartments within the cell that localize intracel- lular enzyme systems so that specific biochemical reactions have a greater possibility of occurring.
• Microtubules are long, hollow-appearing, flexible, tubular structures, composed of a and b tubulin heterodimers (Fig. 2.13A). the tubulin
dimers are arranged in such a fashion that they form gtP-mediated linear assemblies known as protofilaments, and 13 of these protofilaments come together in a cylindrical array to form 25 nm–diameter microtubules whose hollow- appearing center is 15 nm in diameter. each microtubule has a growing, plus end and a minus end that, unless embedded in a cloud of ring-shaped structures composed of g tubulin molecules, would permit the shortening of the microtubule. the plus end is also stabilized by a removable cap that consists of specific
microtubule-associated proteins (MAPs), which prevents the lengthening of the microtubule.
it may be observed that microtubules have a specific polarity. Microtubules can become longer—a process known as rescue—or shorter—a process known as catastrophe—and this cyclic activity is referred to as dynamic instability.
• Additional MAPs act as molecular motor proteins, kinesin and dynein, that allow the microtubules to operate as cellular highways along which cargo is transported long distances toward either the plus end (kinesin) or the minus end (dynein).
• still other MAPs act as spacers between microtubules; some, such as MAP2, keep the microtubules farther apart from each other, whereas others, such as tau, permit
microtubules to be bundled closer to each other.
• Usually, the minus ends of most microtubules of a cell originate from the same region of the cell, known as the centrosome, or the microtubule organizing center (MTOC) of the cell. Microtubules sustain cell morphology, assist in intracellular transport, form the mitotic and meiotic spindle apparatus, form the cores of cilia and flagella, and form centrioles and basal bodies.
• Centrioles are small, cylindrical structures composed of two pairs of nine triplet microtubules where the two centrioles are arranged perpendicular to each other (Fig.
2.13D). During the s-phase of the cell cycle, each component of the pair replicates itself.
centrioles form the centrosome and, during cell division, act as nucleation sites of the spindle apparatus. they also form the basal bodies that direct the development of cilia and flagella.
Chapter Cytoplasm
2
cLINIcAL coNSIDERATIoNS 23
GlycoGen StoraGe DiSorDerS Some individuals have glycogen storage disorders as a result of their inability to degrade glycogen, resulting in excess accumulation of this substance in the cells. There are three classifications of this disease: (1) hepatic, (2) myopathic, and (3) miscellaneous. The lack or malfunction of one of the enzymes responsible for the degradation is responsible for these disorders.
Melanin conDitionS
Individuals who are unable to manufacture melanin, usually because of a genetic mutation involving the enzyme tyrosinase, have very light skin coloration and red eyes. This individuals have albinism. Individuals who produce more than the normal amount of melanin have darker than normal skin and exhibit scalelike patches of dark coloration. These individuals have a condition known as lamellar ichthyosis. Still other individuals may not possess melanocytes, the cells that manufacture melanin. These individuals have a condition known as vitiligo.
Figure 2.13 three-dimensional diagrams of the various components of the cytoskeleton. A, Microtubule. B, thin filament. C, intermediate filament. D, centriole. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed.
Philadelphia, Saunders, 2007, p 43.) A Microtubule
B Thin filaments (actin)
C Intermediate filaments
D Centriole 25 nm
6 nm
5 nm β Tubulin
Cross section Longitudinal view
Actin monomer
Fibrous subunit
(+) End Tubulin dimers (heterodimers)
8–10 nm
0.5 µm
α Tubulin
Chapter Cytoplasm
2
24 • Thin filaments (microfilaments) are composed of G-actin monomers that have assembled (a process requiring AtP) in a polarized fashion into two chains of F-actin filaments coiled around each other, forming a 6-nm-thick filament (see Fig. 2.14B). Actin in its monomeric and filamentous forms constitutes approximately 15% of the protein content of most cells, making it one of the most abundant intracellular
proteins. similar to microtubules, thin filaments have a plus end (barbed because of the presence of the myosin attachment site) and a minus end (pointed because of the absence of myosin attachment site). the lengthening of the filament occurs at a faster pace at the plus end.
• When the thin filament achieves its required length, the two ends are capped by capping proteins, such as gelsolin, which stabilizes both ends of the filament by preventing further polymerization or depolymerization. gelsolin has an additional role of cutting a thin filament in two and capping the severed ends.
• shortening of thin filaments can also occur by the action of cofilin, which induces depolymerization by the removal of g-actin monomers at the minus end. lengthening of thin filaments requires the presence of a pool of g-actin monomers. these monomers are sequestered by thymosin within the cytosol, and the protein profilin facilitates the transfer of g-actin from thymosin to the plus end of the thin filament.
• Branching of thin filaments is regulated by the protein complex, which functions in initiating the attachment of g-actin to an existing thin filament, and from that point on profilin increases the length of the branch. thin filaments form associations with each other that have been categorized into contractile bundles, gel-like networks, and parallel bundles. Actin also participates in the establishment and maintenance of focal contacts of the cell whereby the cell attaches to the extracellular matrix.
• Contractile bundles are associated with myosin i through myosin iX, and function in the contractile process, in muscle contraction or the intracellular movement of cargo.
• Gel-like networks are associated with the protein filamin to form high-viscosity matrices such as those of the cell cortex.
• Parallel bundles are thin filaments associated with the proteins villin and fimbrin, which maintain the thin filaments in a parallel array, such as those of the core of microvilli and microspikes and in the terminal web.
• Intermediate filaments, ropelike structures 8 to 10 nm in diameter, form the framework of the cell, anchor the nucleus in its position, secure integral membrane proteins to the cytoskeleton, and react to extracellular matrix forces.
intermediate filaments (Fig. 2.14c) are composed of rodlike protein tetramers, eight of which form tightly bundled helices of protofilaments. two protofilaments aggregate to form protofibrils, and four of these structures bind to each other to form an intermediate filament. there are about 40 categories of intermediate filaments depending on their polypeptide components and cellular
distribution. the principal classes of intermediate filaments are keratins, desmin, vimentin, glial fibrillary acidic protein, neurofilaments, and nuclear lamins. Intermediate filament binding proteins attach to and bind intermediate filaments to assist in the formation of the three-dimensional cytoskeleton. the best known of these binding proteins are filaggrin, synemin, plectin, and plakins.
• Filaggrins attach keratin filaments to each other to form them into bundles.
• Synemin binds desmin, and plectin binds vimentin to form a three-dimensional framework in the cytosol.
• Plakins attach keratin filaments to hemidesmosomes in epithelial cells and neurofilaments to thin filaments in dorsal ganglion neurons.
cyToSKELEToN (cont.)
Chapter Cytoplasm
2
25
Figure 2.14 three dimensional diagrams of the various components of the cytoskeleton. A, Microtubule. B, thin filament.
C, intermediate filament. D, centriole. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 43.)
A Microtubule
B Thin filaments (actin)
C Intermediate filaments
D Centriole 25 nm
6 nm
5 nm β Tubulin
Cross section Longitudinal view
Actin monomer
Fibrous subunit
(+) End Tubulin dimers (heterodimers)
8–10 nm
0.5 µm
α Tubulin
26
3 NucLEuS
the largest organelle in the cell, the nucleus, not only contains most of the cell’s DnA but also possesses the mechanisms for DnA and RnA syn-
thesis. the nucleus contains three ma jor components: chromatin, the cell’s genetic material; nucleolus, where ri- bo somal RnA (rRnA) is synthesized, and ribosomal subunits are assembled;
and nucleoplasm, a matrix containing various macromolecules and nuclear particles. the nucleus is surrounded by the nuclear envelope composed of two membranes. Although the nucleus may vary in shape, location, and number, in most cells it is centrally located and spherical in shape.