Warming Up

When The Doctor was preparing a drug that would be injected to the patient, suddenly, the patient who was lying in bed screaming out. The Doctor was surprised, so he asked to the patient: 

The Doctor : Well...why are you screaming out ? What is the fear of injections ? 
Patients : No...Sir, I screamed just for warming up. So that, when I'm shot I will not scream anymore... :D 
The Doctor : ?!!?!!?!?!

Cytosol

 At one time, it was believed that the cytoplasm intervening between the discrete organelles and deposits was unstructured. This belief was reinforced by the use of homogenization and centrifugation of the homogenates to yield fractions consisting of recognizable membrane-bound organelles. The final supernatant produced by this process, after the separation of organelles, is called the cytosol. The cytosol constitutes about half the total volume of the cell. Homogenization of cells disrupts a delicate microtrabecular lattice that incorporates filaments of actin, microtubules, intermediate filaments, enzymes, and other soluble constituents into a structured cytosol. The cytosol coordinates the intracellular movements of organelles and provides an explanation for the viscosity of the cytoplasm. Soluble (not membrane-bound) enzymes, such as those of the glycolytic pathway, for example, function more efficiently when organized in a sequence instead of having to rely on random collisions with their substrates. The cytosol provides a framework for this organization. It contains thousands of enzymes that produce building blocks for larger molecules and break down small molecules to liberate energy. All machinery to synthesize proteins (rRNA, mRNA, tRNA, enzymes, and other factors) is contained in the cytosol.

Cell Components & Diseases

Many diseases are related to molecular alterations in specific cell components. In several of these diseases, structural changes can be detected by light or electron microscopy or by cytochemical techniques. Table 2–5 lists some of these diseases and emphasizes the importance of understanding the many cell components in pathobiology. Table 2–5. Some Human and Animal Diseases Related to Altered Cellular Components. Cell Component Involved Disease Molecular Defect Morphological Change Clinical Consequence Mitochondrion Mitochondrial cytopathy Defect of oxidative phosphorylation Increase in size and number of muscle mitochondria High basal metabolism without hyperthyroidism Microtubule Immotile cilia syndrome Lack of dynein in cilia and flagella Lack of arms of the doublet microtubules Immotile cilia and flagella with male sterility and chronic respiratory infection Mouse (Acomys) diabetes   Reduction of tubulin in pancreatic cells Reduction of microtubules in cells High blood sugar content (diabetes) Lysosome Metachromatic leukodystrophy Lack of lysosomal sulfatase Accumulation of lipid (cerebroside) in tissues Motor and mental impairment Hurler disease Lack of lysosomal -L-iduronidase  Accumulation of dermatan sulfate in tissues Growth and mental retardation Golgi complex I-cell disease Phosphotransferase deficiency Inclusion-particle storage in several cells Psychomotor retardation, bone abnormalities

References Afzelius BA, Eliasson R: Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. J Ultrastruct Res 1979;69:43. [PMID: 501788] Aridor M, Balch WE: Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745. [PMID: 10395318] Barrit GJ: Communication Within Animal Cells. Oxford University Press, 1992. Becker WM et al: The World of the Cell, 4th ed. Benjamin/Cummings, 2000. Bretscher MS: The molecules of the cell membrane. Sci Am 1985;253:100. [PMID: 2416050] Brinkley BR: Microtubule organizing centers. Annu Rev Cell Biol 1985;1:145. [PMID: 3916316] Brown MS et al: Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell 1983;32:663. [PMID: 6299572] Cooper GM: The Cell: A Molecular Approach. ASM Press/Sinauer Associates, Inc., 1997. DeDuve C: A Guided Tour of the Living Cell. Freeman, 1984. DeDuve C: Microbodies in the living cell. Sci Am 1983;248:74. Dustin P: Microtubules, 2nd ed. Springer-Verlag, 1984. Farquhar MG: Progress in unraveling pathways of Golgi traffic. Annu Rev Cell Biol 1985;1:447. [PMID: 3916320] Fawcett D: The Cell, 2nd ed. Saunders, 1981. Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979. Mitchison TJ, Cramer LP: Actin-based cell motility and cell locomotion. Cell 1996;84:371. [PMID: 8608590] Osborn M, Weber K: Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303. [PMID: 6891619] Pfeffer SR, Rothman JE: Biosynthetic protein transport and sorting in the endoplasmic reticulum. Annu Rev Biochem 1987;56:829. [PMID: 3304148] Rothman J: The compartmental organization of the Golgi apparatus. Sci Am 1985;253:74. [PMID: 3929377] Simons K, Ikonen E: How cells handle cholesterol. Science 2000;290:1721. [PMID: 11099405] Tzagoloff A: Mitochondria. Plenum, 1982. Weber K, Osborn M: The molecules of the cell matrix. Sci Am 1985;253:110. [PMID: 4071030]

Cytoplasmic Deposits

Cytoplasmic deposits are usually transitory components of the cytoplasm, composed mainly of accumulated metabolites or other substances. The accumulated molecules occur in several forms, one of them being lipid droplets in adipose tissue, adrenal cortex cells, and liver cells (Figure 2–38). Carbohydrate accumulations are also visible in several cells in the form of glycogen. After impregnation with lead salts, glycogen appears as collections of electron-dense particles (Figure 2–39). Proteins are stored in glandular cells as secretory granules or secretory vesicles (Figure 2–29); under stimulation, these proteins are periodically released into the extracellular medium.

Figure 2-38

Section of adrenal gland showing lipid droplets (L) and abundant anomalous mitochondria (M). x19,000. Figure 2-39 Electron micrograph of a section of a liver cell showing glycogen deposits as accumulations of electron-dense particles (arrows). The dark structures with a dense core are peroxisomes. Mitochondria (M) are also shown. x30,000. Deposits of colored substances—pigments—are often found in cells (Figure 2–40). They may be synthesized by the cell (eg, in the skin melanocytes) or come from outside the body (eg, carotene). One of the most common pigments is lipofuscin, a yellowish-brown substance present mainly in permanent cells (eg, neurons, cardiac muscle) that increases in quantity with age. Its chemical constitution is complex. It is believed that granules of lipofuscin derive from secondary lysosomes and represent deposits of indigestible substances. A widely distributed pigment, melanin is abundant in the epidermis and in the pigment layer of the retina in the form of dense intracellular membrane-limited granules. Figure 2-40 Section of amphibian liver shows cells with pigment deposit (PD) in the cytoplasm, a macrophage (M), hepatocytes (H), and a neutrophil leukocyte (N). In this resin-embedded material it is possible to see mitochondria (pale red) and lysosomes (blue) in the cytoplasm of the hepatocytes. Only with resin embedding is it possible to obtain such information. Giemsa stain. Medium magnification. References Afzelius BA, Eliasson R: Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. J Ultrastruct Res 1979;69:43. [PMID: 501788] Aridor M, Balch WE: Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745. [PMID: 10395318] Barrit GJ: Communication Within Animal Cells. Oxford University Press, 1992. Becker WM et al: The World of the Cell, 4th ed. Benjamin/Cummings, 2000. Bretscher MS: The molecules of the cell membrane. Sci Am 1985;253:100. [PMID: 2416050] Brinkley BR: Microtubule organizing centers. Annu Rev Cell Biol 1985;1:145. [PMID: 3916316] Brown MS et al: Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell 1983;32:663. [PMID: 6299572] Cooper GM: The Cell: A Molecular Approach. ASM Press/Sinauer Associates, Inc., 1997. DeDuve C: A Guided Tour of the Living Cell. Freeman, 1984. DeDuve C: Microbodies in the living cell. Sci Am 1983;248:74. Dustin P: Microtubules, 2nd ed. Springer-Verlag, 1984. Farquhar MG: Progress in unraveling pathways of Golgi traffic. Annu Rev Cell Biol 1985;1:447. [PMID: 3916320] Fawcett D: The Cell, 2nd ed. Saunders, 1981. Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979. Mitchison TJ, Cramer LP: Actin-based cell motility and cell locomotion. Cell 1996;84:371. [PMID: 8608590] Osborn M, Weber K: Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303. [PMID: 6891619] Pfeffer SR, Rothman JE: Biosynthetic protein transport and sorting in the endoplasmic reticulum. Annu Rev Biochem 1987;56:829. [PMID: 3304148] Rothman J: The compartmental organization of the Golgi apparatus. Sci Am 1985;253:74. [PMID: 3929377] Simons K, Ikonen E: How cells handle cholesterol. Science 2000;290:1721. [PMID: 11099405] Tzagoloff A: Mitochondria. Plenum, 1982. Weber K, Osborn M: The molecules of the cell matrix. Sci Am 1985;253:110. [PMID: 4071030]

Intermediate Filaments

Ultrastructural and immunocytochemical investigations reveal that a third major filamentous structure is present in eukaryotic cells. In addition to the thin (actin) and thick (myosin) filaments, cells contain a class of intermediate-sized filaments with an average diameter of 10–12 nm (Figure 2–37 and Table 2–4). Several proteins that form intermediate filaments have been isolated and localized by immunocytochemical means.

Figure 2-37

Electron micrograph of a skin epithelial cell showing intermediate filaments of keratin associated with desmosomes.

Table 2–4. Examples of Intermediate Filaments Found in Eukaryotic Cells.

Filament Type Cell Type Examples Keratins Epithelium Both keratinizing and nonkeratinizing epithelia Vimentin Mesenchymal cells Fibroblasts, chondroblasts, macrophages, endothelial cells, vascular smooth muscle Desmin Muscle Striated and smooth muscle (except vascular smooth muscle) Gilial fibrillary acidic proteins Glial cells Astrocytes Neurofilaments Neurons Nerve cell body and processes

Keratins (Gr. keras, horn) are a family of approximately 20 proteins found in epithelia. They are encoded by a family of genes and have different chemical and immunological properties. This diversity of keratin is related to the various roles these proteins play in the epidermis, nails, hooves, horns, feathers, scales, and the like that provide animals with defense against abrasion and loss of water and heat.

Vimentin filaments are characteristic of cells of mesenchymal origin. (Mesenchyme is an embryonic tissue.) Vimentin is a single protein (56–58 kDa) and may copolymerize with desmin or glial fibrillary acidic protein.

Desmin (skeletin) is found in smooth muscle and in the Z disks of skeletal and cardiac muscle (53–55 kDa).

Glial filaments (glial fibrillary acidic protein) are characteristic of astrocytes but are not found in neurons, muscle, mesenchymal cells, or epithelia (51 kDa).

Neurofilaments consist of at least three high-molecular-weight polypeptides (68, 140, and 210 kDa). Intermediate filament proteins have different chemical structures and different roles in cellular function.

Medical Application

The presence of a specific type of intermediate filament in tumors can reveal which cell originated the tumor, information important for diagnosis and treatment (see Table 1–1). Identification of intermediate filament proteins by means of immunocytochemical methods is a routine procedure.

References

Afzelius BA, Eliasson R: Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. J Ultrastruct Res 1979;69:43. [PMID: 501788]

Aridor M, Balch WE: Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745. [PMID: 10395318]

Barrit GJ: Communication Within Animal Cells. Oxford University Press, 1992.

Becker WM et al: The World of the Cell, 4th ed. Benjamin/Cummings, 2000.

Bretscher MS: The molecules of the cell membrane. Sci Am 1985;253:100. [PMID: 2416050]

Brinkley BR: Microtubule organizing centers. Annu Rev Cell Biol 1985;1:145. [PMID: 3916316]

Brown MS et al: Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell 1983;32:663. [PMID: 6299572]

Cooper GM: The Cell: A Molecular Approach. ASM Press/Sinauer Associates, Inc., 1997.

DeDuve C: A Guided Tour of the Living Cell. Freeman, 1984.

DeDuve C: Microbodies in the living cell. Sci Am 1983;248:74.

Dustin P: Microtubules, 2nd ed. Springer-Verlag, 1984.

Farquhar MG: Progress in unraveling pathways of Golgi traffic. Annu Rev Cell Biol 1985;1:447. [PMID: 3916320]

Fawcett D: The Cell, 2nd ed. Saunders, 1981.

Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979.

Mitchison TJ, Cramer LP: Actin-based cell motility and cell locomotion. Cell 1996;84:371. [PMID: 8608590]

Osborn M, Weber K: Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303. [PMID: 6891619]

Pfeffer SR, Rothman JE: Biosynthetic protein transport and sorting in the endoplasmic reticulum. Annu Rev Biochem 1987;56:829. [PMID: 3304148]

Rothman J: The compartmental organization of the Golgi apparatus. Sci Am 1985;253:74. [PMID: 3929377]

Simons K, Ikonen E: How cells handle cholesterol. Science 2000;290:1721. [PMID: 11099405]

Tzagoloff A: Mitochondria. Plenum, 1982.

Weber K, Osborn M: The molecules of the cell matrix. Sci Am 1985;253:110. [PMID: 4071030]

Actin Filaments

Contractile activity in muscle cells results primarily from an interaction between two proteins: actin and myosin. Actin is present in muscle as a thin (5–7 nm in diameter) filament composed of globular subunits organized into a double-stranded helix (Figure 2–36). Structural and biochemical studies reveal that there are several types of actin and that this protein is present in all cells.

Figure 2-36

The cytosolic actin filament. Actin dimers are added to the plus (+) end and removed at the minus (–) end, dynamically lengthening or shortening the filament, as required by the cell. (Redrawn and reproduced, with permission, from Junqueira LC, Carneiro J: Biologia Celular e Molecular, 6th ed. Editora Guanabara, 1997.)

Within cells, microfilaments can be organized in many forms.

1. In skeletal muscle, they assume a paracrystalline array integrated with thick (16-nm) myosin filaments.

2. In most cells, actin filaments form a thin sheath just beneath the plasmalemma, called the cell cortex. These filaments appear to be associated with membrane activities such as endocytosis, exocytosis, and cell migratory activity.

3. Actin filaments are intimately associated with several cytoplasmic organelles, vesicles, and granules. The filaments are believed to play a role in moving and shifting cytoplasmic components (cytoplasmic streaming).

4. Actin filaments are associated with myosin and form a "purse-string" ring of filaments whose constriction results in the cleavage of mitotic cells.

5. In most cells, actin filaments are found scattered in what appears to be an unorganized fashion within the cytoplasm (Figure 2–31).

Although actin filaments in muscle cells are structurally stable, in nonmuscle cells they readily dissociate and reassemble. Actin filament polymerization appears to be under the direct control of minute changes in Ca²⁺ and cyclic AMP levels. A large number of actin-binding proteins have been demonstrated in a wide variety of cells, and much current research is focused on how these proteins regulate the state of polymerization and lateral aggregation of actin filaments. Their importance can be deduced from the fact that only about half the cell's actin is in the form of filaments.

Presumably, most actin filament-related activities depend upon the interaction of myosin with actin. (The structure and activity of the thick myosin filaments are described in the section on muscle tissues.)

References

Afzelius BA, Eliasson R: Flagellar mutants in man: on the heterogeneity of the immotile-cilia syndrome. J Ultrastruct Res 1979;69:43. [PMID: 501788]

Aridor M, Balch WE: Integration of endoplasmic reticulum signaling in health and disease. Nat Med 1999;5:745. [PMID: 10395318]

Barrit GJ: Communication Within Animal Cells. Oxford University Press, 1992.

Becker WM et al: The World of the Cell, 4th ed. Benjamin/Cummings, 2000.

Bretscher MS: The molecules of the cell membrane. Sci Am 1985;253:100. [PMID: 2416050]

Brinkley BR: Microtubule organizing centers. Annu Rev Cell Biol 1985;1:145. [PMID: 3916316]

Brown MS et al: Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell 1983;32:663. [PMID: 6299572]

Cooper GM: The Cell: A Molecular Approach. ASM Press/Sinauer Associates, Inc., 1997.

DeDuve C: A Guided Tour of the Living Cell. Freeman, 1984.

DeDuve C: Microbodies in the living cell. Sci Am 1983;248:74.

Dustin P: Microtubules, 2nd ed. Springer-Verlag, 1984.

Farquhar MG: Progress in unraveling pathways of Golgi traffic. Annu Rev Cell Biol 1985;1:447. [PMID: 3916320]

Fawcett D: The Cell, 2nd ed. Saunders, 1981.

Krstíc RV: Ultrastructure of the Mammalian Cell. Springer-Verlag, 1979.

Mitchison TJ, Cramer LP: Actin-based cell motility and cell locomotion. Cell 1996;84:371. [PMID: 8608590]

Osborn M, Weber K: Intermediate filaments: cell-type-specific markers in differentiation and pathology. Cell 1982;31:303. [PMID: 6891619]

Pfeffer SR, Rothman JE: Biosynthetic protein transport and sorting in the endoplasmic reticulum. Annu Rev Biochem 1987;56:829. [PMID: 3304148]

Rothman J: The compartmental organization of the Golgi apparatus. Sci Am 1985;253:74. [PMID: 3929377]

Simons K, Ikonen E: How cells handle cholesterol. Science 2000;290:1721. [PMID: 11099405]

Tzagoloff A: Mitochondria. Plenum, 1982.

Weber K, Osborn M: The molecules of the cell matrix. Sci Am 1985;253:110. [PMID: 4071030]