Important Points: Nuclear Structures

BARR BODY
• Careful study of the chromatin of mammalian cell nuclei reveals a heterochromatin mass that is frequently observed in female cells but not in male cells. This chromatin clump is the sex chromatin and is one of the two X chromosomes present in female cells. The X chromosome that constitutes the sex chromatin remains tightly coiled and visible, whereas the other X chromosome is uncoiled and not visible. Evidence suggests that the sex chromatin is genetically inactive. The male has one X chromosome and one Y chromosome as sex determinants; the X chromosome is uncoiled, and therefore no sex chromatin is visible. In human epithelial cells, sex chromatin appears as a small granule attached to the nuclear envelope. The cells lining the internal surface of the cheek are frequently used to study sex chromatin. Blood smears are also often used, in which case the sex chromatin appears as a drumsticklike appendage to the nuclei of the neutrophilic leukocytes.

BARR BODY

• CLINICAL CORELATES:
• The study of sex chromatin discloses the genetic sex in patients whose external sex organs do not permit assignment of gender, as in hermaphroditism and pseudohermaphroditism. Sex chromatin helps the study of other anomalies involving the sex chromosomesKlinefelter syndrome, in which testicular abnormalities, azoospermia (absence of spermatozoa), and other symptoms are associated with the presence of XXY chromosomes

• Nucleolus
• Many nuclei, especially those of cells highly active in protein synthesis, contain one or more dense structures called nucleoli which are the sites of ribosomal RNA synthesis and ribosome assembly. Ribosomal RNA and proteins, synthesised in the cytoplasm and imported back into the nucleus, are assembled into subunits. The subunits then pass back to the cytoplasm to aggregate into complete ribosomes. This micrograph shows a typical nucleolus.

Electron microscopy shows three regions of nucleolus.

Types of RNAs
• Note that RNA is of three types. • rRNA (ribosomal RNA) synthesized by RNA Polymerase I • mRNA (messenger RNA) synthesized by RNA Polymerase II • tRNA (transfer RNA) synthesized by RNA Polymerase III

NUCLEAR ENVELOPE, CHROMATIN ,NUCLEOLUS

Liver cells (hepatocytes). Several dark-stained nuclei are shown. Note the apparent nuclear membrane consisting mainly of a superficial condensation of chromatin. Several nucleoli are seen inside the nuclei, suggesting intense protein synthesis. One hepatocyte contains two nuclei.

Schematic representation of a cell nucleus. The nuclear envelope is composed of two membranes of the endoplasmic reticulum, enclosing a perinuclear cisterna. Where the two membranes fuse, they form nuclear pores. Ribosomes are attached to the outer nuclear membrane. Heterochromatin clumps are associated with the nuclear lamina, whereas the euchromatin (EC) appears dispersed in the interior of the nucleus. In the nucleolus, note the associated chromatin, heterochromatin (Hc), the pars granulosa (G), and the pars fibrosa (F).

Nuclear Envelope
Electron microscopy shows that the nucleus is surrounded by two parallel membranes separated by a narrow space (40?0 nm) called the perinuclear cisterna .Together, the paired membranes and the intervening space make up the nuclear envelope. At sites at which the inner and outer membranes of the nuclear envelope fuse, there are gaps, the nuclear pores (Figures 3鈥? and 3鈥?), that provide controlled pathways between the nucleus and the cytoplasm.

Label the Diagram

Detailed look of Nuclear pore
Illustration showing the structure, the localization, and the relationship of the nuclear lamina with chromosomes. The drawing also shows that the nuclear pore complex is composed of two protein rings in an octagonal organization. From the cytoplasmic ring, long filaments penetrate the cytosol, and from the intranuclear ring arise filaments that constitute a basketlike structure. The presence of the central cylindrical granule in the nuclear pore is not universally accepted.

Electron micrograph obtained by cryofracture of a rat intestine cell, showing the two components of the nuclear envelope and the nuclear pores.(studies elements under extremely cold temperature generally using liquid nitrogen)

DNA ARRANGEMENT
The orders of chromatin packing believed to exist in the metaphase chromosome. Starting at the top, the 2-nm DNA double helix is shown; next is the association of DNA with histones to form filaments of nucleosomes of 11 nm and 30 nm. Through further condensation, filaments with diameters of 300 nm and 700 nm are formed. Finally, the bottom drawing shows a metaphase chromosome, which exhibits the maximum packing of DNA.

CELL DIVISION
• The phase between two mitoses is called INTERPHASE, during which the nucleus appears as it is normally observed in microscopic preparations.

• The PROPHASE of mitosis is characterized by the gradual coiling of nuclear chromatin (uncoiled chromosomes), giving rise to several individual rod- or hairpin-shaped bodies (coiled chromosomes) that stain intensely.

During METAPHASE, • chromosomes, due to the activity of microtubules, migrate to the equatorial plane of the cell, where each divides longitudinally to form two chromosomes called sister chromatids. The chromatids attach to the microtubules of the mitotic spindle.

ANAPHASE In , the sister chromatids • separate from each other and migrate toward the opposite poles of the cell, pulled by microtubules. Throughout this process, the centromeres move away from the center, pulling the remainder of the chromosome along. The centromere is the constricted region of a mitotic chromosome that holds the two sister chromatids together until the beginning of anaphase.

TELOPHASE is characterized by the reappearance of nuclei in the daughter cells. The chromosomes revert to their semidispersed state, and the nucleoli, chromatin, and nuclear envelope reappear. While these nuclear alterations are taking place, a constriction develops at the equatorial plane of the parent cell and progresses until the cytoplasm and its organelles are divided in two. This constriction is produced by microfilaments of actin associated with myosin that accumulate in a beltlike shape beneath the cell membrane.

THE CELL CYCLE

G1 PHASE
The first phase within interphase, from the end of the previous M phase until the beginning of DNA synthesis is called G1 (G indicating gap). It is also called the growth phase. During this phase the biosynthetic activities of the cell, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication. Duration of G1 is highly variable, even among different cells of the same species.

S PHASE
The ensuing S phase starts when DNA synthesis commences; when it is complete, all of the chromosomes have been replicated, i.e., each chromosome has two (sister) chromatids. Thus, during this phase, the amount of DNA in the cell has effectively doubled, though the ploidy of the cell remains the same. Rates of RNA transcription and protein synthesis are very low during this phase. An exception to this is histone production, most of which occurs during the S phase.

G2 PHASE
The cell then enters the G2 phase, which lasts until the cell enters mitosis. Again, significant protein synthesis occurs during this phase, mainly involving the production of microtubules, which are required during the process of mitosis. Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis.

MITOSIS (M PHASE)

The relatively brief M phase consists of nuclear division (karyokinesis) and cytoplasmic division (cytokinesis) G0 PHASE: In cells that are not continuously dividing, the activities of the cell cycle may be temporarily or permanently suspended. Cells in such a state (eg, muscle, nerve) are referred to as being in the G0 phase.

CLINICAL :
Growth factors stimulates increase cell cycle rate thus increase the cell production e.g.. Erythropoietin. In Cancers the cell cycle is abnormally increased thus uncontrolled cell production. Some Anticancer drugs act by controlling this uncontrolled rate.

MITOCHONDRIA

• Three-dimensional representation of a mitochondrion with its cristae penetrating the matrix space. Note that two membranes delimiting an intermembrane space form the wall of the mitochondrion. The cristae are covered with globular units that participate in the formation of ATP.

(A) the concept that cells synthesizing proteins (represented here by spirals) that are to remain within the cytoplasm possess (free) polyribosomes (ie, nonadherent to the endoplasmic reticulum). In B, where the proteins are segregated in the endoplasmic reticulum and may eventually be extruded from the cytoplasm (export proteins), not only do the polyribosomes adhere to the membranes of rough endoplasmic reticulum, but the proteins produced by them are injected into the interior of the organelle across its membrane. In this way, the proteins, especially enzymes such as ribonucleases and proteases, which could have undesirable effects on the cytoplasm, are separated from it.

a cell that synthesizes, segregates, and directly exports proteins (C); and a cell that synthesizes, segregates, stores in supranuclear granules, and exports proteins (D).

Three-dimensional representation of a Golgi complex. Through transport vesicles that fuse with the Golgi cis face, the complex receives several types of molecules produced in the rough endoplasmic reticulum (RER). After Golgi processing, these molecules are released from the Golgi trans face in larger vesicles to constitute secretory vesicles, lysosomes, or other cytoplasmic components.

Photomicrograph of a kidney tubule whose lumen appears in the center as a long slit. The numerous dark-stained cytoplasmic granules are lysosomes (L), organelles abundant in these kidney cells. The cell nuclei (N), some showing a nucleolus, are also seen in the photograph as dark-stained corpuscles.

CLINICAL:
The antimitotic alkaloids are useful tools in cell biology (eg, colchicine is used to arrest chromosomes in metaphase and to prepare karyotypes) and in cancer chemotherapy (eg, vinblastine, vincristine, and taxol are used to arrest cell proliferation in tumors). Because tumor cells proliferate rapidly, they are more affected by antimitotic drugs than are normal cells. However, chemotherapy has many undesirable consequences. For example, some normal blood-forming cells and the epithelial cells that cover the digestive tract also show a high rate of proliferation and are adversely affected by chemotherapy.

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.

Cytoplasmic Deposits

SEROUS CELLS
The acinar cells of the pancreas and parotid salivary glands are examples of serous cells. They are polyhedral or pyramidal, with central, rounded nuclei. Their polarity is well defined. In the basal region, serous cells exhibit an intense basophilia, which results from local accumulation of RNA present in polyribosomes apposed to abundant parallel arrays of cisternae of rough endoplasmic reticulum .Between the nucleus and the free surface lies a welldeveloped Golgi complex

Serous secretory cells of the pancreas disposed in acini. One acinus is depicted by a broken line. The basophilic basal region of each cell is rich in RNA and the apex contains light-stained secretory vesicles.

MUCUS-SECRETING CELLS The most thoroughly studied mucus-secreting cell is the goblet cell of the intestines .This cell has numerous large, lightly staining granules containing strongly hydrophilic glycoproteins called mucins. Secretory granules fill the extensive apical pole of the cell, and the nucleus is located in the cell base, which is rich in rough endoplasmic reticulum. The Golgi complex, located just above the nucleus, is exceptionally well developed, indicative of its important function in this cell.

Mucous secretory gland of the esophagus whose cells have a clear cytoplasm and basal dark-stained nuclei. The lumen of the gland is clearly seen (short arrows). The long arrow indicates a secretory duct.

STEROID-SECRETING CELLS
Cells that secrete steroids are found in various organs of the body (eg, testes, ovaries, adrenals). They are endocrine cells specialized for synthesizing and secreting steroids with hormonal activity. They have abundance of the smooth endoplasmic reticulum (SER), lipid droplets, Golgi complex, and lysosomes. The numerous mitochondria have mainly tubular cristae. They not only produce the energy necessary for the activity of the cell but are also involved in steroid hormone synthesis. Rough endoplasmic reticulum (RER) is also shown.

STEROID SECRETING CELL:
Electron micrograph of a section of an interstitial cell from Testis. There is abundant smooth endoplasmic reticulum as well as mitochondria. Steroid secreting.

MUCUS-SECRETING CELLS

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