Basic Cell Biology

Basic Cell Biology I. Cytoplasm A. Plasma membrane B. Mitochondria C. Ribosomes D. Endoplasmic reticulum 1. Rough 2. Smooth E. Golgi apparatus F. Lysosomes G. Cytoskeleton II. Nucleus A. Nuclear Envelope B. Chromatin C. Nucleolus D. Nuclear matrix III. Cell division © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Asymmetrical arrangement of phospholipids in plasma membrane „ ATP-dependent phospholipid translocase Molecular Cell Biology, Lodish et al., 4th edition. Figure 2—1. The ultrastructure and molecular organization (right) of the cell membrane. The dark lines at left represent the two dense layers observed in the electron microscope; these are caused by the deposit of osmium in the hydrophilic portions of the phospholipid molecules. © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Figure 11—14. Electron micrograph of a transverse section of a continuous capillary. Note the nucleus (N) and the junctions between neighboring cells (arrowheads). Numerous pinocytotic vesicles are evident (small arrows). C. Ribosomes „ Structure- 2 subunits, composed of 4 types of RNA and 80 different proteins. … RNA is synthesized in the nucleolus … Protein is synthesized in the cytoplasm. „ Characteristics … Ribosomes are very basophilic, stain with hematoxylin , toluidine blue … Found in clusters called polyribosomes that are held together by a strand of RNA. mRNA Ribosome Polyribosomes Ribosome function „ Translation of mRNA into protein „ Free polyribosomes- synthesize proteins used in the cytoplasm „ Polyribosomes attached to the ER- used to synthesize „ Secreted proteins „ Integral membrane proteins „ Lysosomal proteins Three dimensional ribosome structure, L1 is a ribosomal protein © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. •Ribosome-two thirds RNA, one third protein •Each ribosome has three binding sites for tRNA, and a binding site for mRNA © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Endoplasmic Reticulum „ Segregation of newly synthesized proteins from the cytoplasm „ Glycosylation of certain proteins „ Lipid synthesis RER structure „ RER … Contains polyribosomes, very basophilic … Prominent in protein synthesizing cells „ Functions … Synthesize proteins with the following destinations: „ Storage in lysosomes „ Storage in secretory granules „ Use as integral proteins SRP- 6 non-identical proteins, 7 S RNA © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Figure 2—19. The ultrastructure of a cell that synthesizes (but does not secrete) proteins on free polyribosomes (A); a cell that synthesizes, segregates, and stores proteins in organelles (B); a cell that synthesizes, segregates, and directly exports proteins (C); and a cell that synthesizes, segregates, stores in supranuclear granules, and exports proteins (D). SER „ Structure …Lacks polyribosomes, hard to see at light microscope level „ Function …Detoxification (liver) …Steroid synthesis (gonad, adrenal) …Ca2+ reservoir in skeletal muscle Golgi apparatus „ Posttranslational processing including glycosylation, phosphorylation, proteolysis „ Packing and concentration of secretory granules Apical Basal Lysosomes „ Membrane bound vesicles that contain hydrolytic enzymes for digestion „ Heterophagy … Digestion of extracellular material „ Autophagy digestion of intracellular organelles „ Review Table 2-3 for clinical correlations … Eg. Tay-Sachs disease- accumulation of glycolipid in nerves Figure 2—27. Current concepts of the functions of lysosomes. Synthesis occurs in the rough endoplasmic reticulum (RER), and the enzymes are packaged in the Golgi complex. Note the heterophagosomes, in which bacteria are being destroyed, and the autophagosomes, with RER and mitochondria in the process of digestion. Heterophagosomes and autophagosomes are secondary lysosomes. The result of their digestion can be excreted, but sometimes the secondary lysosome creates a residual body, containing remnants of undigested molecules. In some cells, such as osteoclasts, the lysosomal enzymes are secreted to the extracellular environment. Nu, nucleolus. Cytoskeleton „ Microtubules „ Microfilaments „ Intermediate filaments „ Function …Maintain cell shape … Cell movement (diapedesis) … Cytoplasm movement (ie. transport of secretory granules) Microtubules „ Polymers of the protein tubulin „ Intracellular movement „ Form centrioles … 9 microtubules triplets „ Form cilia and flagella … 9 microtubules pairs called axonemes surrounding two central microtubules „ Immotile cilia syndrome of Kartagener Microfilaments „ Eg. Actin, @ 6-8 nm thick „ Most cells have actin to some extent Intermediate filaments „ Table 2-4 „@ 10 nm diameter „ Lamin, nuclear envelope protein „ GFAP, glial fibrillary acidic protein, glial cells (astrocytes) 10 nm © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Nuclear envelope „ Invisible with light microscope „ Nuclear pores- areas of fusion between two sheaths of nuclear envelope …< 10 nm pass freely through „ Selective barrier between nuclear contents and cytoplasm RER Nuclear pore Nuclear envelope Perinuclear space Figure 3—5. Illustration to show the structure, the localization, and the relationship of the nuclear lamina with chromosomes. The drawing also shows that the nuclear pore complex is made of 2 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. Figure 3—6. Electron micrographs of nuclei showing their envelopes composed of 2 membranes and the nuclear pores (arrows). The two upper pictures are of transverse sections; the bottom is of a tangential section. Chromatin, frequently condensed below the nuclear envelope, is not usually seen in the pore regions. x80,000. Figure 3—7. Electron micrograph obtained by cryofracture of a rat intestine cell, showing the two components of the nuclear envelope and the nuclear pores. (Courtesy of P Pinto da Silva.) © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Nuclear lamina „ Fibrous, between nuclear envelope and chromatin „ Composed of intermediate filaments- lamins „ Pulls nucleus back together during telophase © 2000 by Geoffrey M. Cooper Phosphorylation of lamins causes dissolution Chromatin „ Heterochromatin- very e- dense, basophilic „ Euchromatin- very light staining „ Can be used to determine cell activity …Light staining- active …Dark staining- not active Figure 3—9. Schematic representation of a nucleosome. This structure consists of a core of 4 types of histones (2 copies of each)– H2A, H2B, H3, and H4–and one molecule of H1 or H5 located outside the DNA filament. Figure 3—10. 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. Nucleolus „ Spherical, lots of RNA and protein „ Very basophilic „ Site of ribosome synthesis Cell division (mitosis) © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Figure 3—12. Human karyotype preparation made by means of a banding technique. Each chromosome has a particular pattern of banding that facilitates its identification and also the relationship of the banding pattern to genetic anomalies. The chromosomes are grouped in numbered pairs according to their morphologic characteristics. Figure 3—16. Photomicrograph of cultured cells to show cell division. Picrosirius-hematoxylin stain. Medium magnification. A: Interphase nuclei. Note the chromatin and nucleoli inside each nucleus. B: Prophase. No distinct nuclear envelope, no nucleoli. Condensed chromosomes. C: Metaphase. The chromosomes are located in a plate at the cell equator. D: Late anaphase. The chromosomes are located in both cell poles, to distribute the DNA equally between the daughter cells. Figure 3—18. Electron micrograph of a section of a rooster spermatocyte in metaphase. The figure shows the two centrioles in each pole, the mitotic spindle formed by microtubules, and the chromosomes in the equatorial plane. The arrows show the insertion of microtubules in the centromeres. Reduced from x19,000. (Courtesy of R McIntosh.) Interphase „ G1- RNA, protein synthesis „ S- DNA synthesis „ G2-cell growth, synthesis of tubulin, energy substrates Figure 3—21. The 4 phases of the cell cycle. In G1 the cell either continues the cycle or enters a quiescent phase called G0. From this phase, most cells can return to the cycle, but some stay in G0 for a long time or even for their entire lifetime. The checking or restriction point (R) in G1 stops the cycle under conditions unfavorable to the cell. When the cell passes this restriction point, it continues the cycle through the synthetic phase (S) and the G2 phase, originating 2 daughter cells in mitosis (M) except when interrupted by another restriction point (not shown) in G2. Figure 3—20. Phases of the cell cycle in bone tissue. The G1 phase (presynthesis) varies in duration, which depends on many factors, including the rate of cell division in the tissue. In bone tissue, G1 lasts 25 h. The S phase (DNA synthesis) lasts about 8 h. The G2-plus-mitosis phase lasts 2.5—3 h. (The times indicated are courtesy of RW Young.)