Cell Bio Chapter 20 Tissues, Stem cells and Cancer highlighted and starred notes

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Cell Bio Chapter 20 Tissues, Stem cells and Cancer highlighted and starred notes
2013-12-11 18:42:16
cell bio

cell bio final ch. 20 davis
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  1. Four types of tissues
    • Connective
    • epithelial
    • nervous
    • muscular
  2. Connective tissue and extracellular matrix perform
    attachment and organizational functions for the other three types of tissues
  3. Connective tissues vary in
    • strength, elasticity, and other structural parameters.
    • however all tissues have collagen
  4. Collagen
    • structural protein
    • collagen forms multimer of single polypeptide chains initially coiled as a triple helix. These helical trimmers are then packed into collagen fibrils, which then comprise fibers of 0.5-3 um in diameter
  5. Fibroblasts
    • secrete collagen and other components of extracellular matrix
    • these cells are easy to culture but must use trypsin or other proteases due to strong attachment to ECM
    • secrete procollagen which is then convereted to collagen, and then arranged into collagen fibers as required by tissues (can be observed in tissue culture on collagen coated plastic)
  6. Skin connective tissue
    collagen fibers are laid down at 90 degree angles to each other to create a plywood-like composite structure
  7. ECM cross-linking proteins
    fibronectin and various integrins are present in ECM as strong linkages
  8. Fibronectin
    • dimeric protein connected at its C terminal end by dual disulphide linkages.
    • each monomer contains binding sites for collagen and integrins.
  9. Integrins
    • integral membrane proteins, and some are embedded in membrane
    • can transmit signals to interior of the cells to induce growth, replication, or apoptosis
    • Humans have 24 types of integrins which are used by differ cell types
    • when activated, integrin dimers can bind to attachment sites on fibronectin and to intracellular actin filaments via adaptor proteins. cell is then indirectly anchored to collagen fibril by cytoskeleton.
  10. Integrin activation
    • modulation of integrin action can occur extracellularly (outside-in activation) or intracellularly (insdie-out activation)
    • either case a conformational change of an integrin dimer activates it to bind strongly to the ECM and to the cytoskeleton.
  11. Proteoglycans
    • provide compressive resistance by filling in the rest of the ECM
    • consist of various proteins linked to complex, branched polysaccharides called glycosaminoglycans (GAGs)
    • proteoglycans are extremely diverse, and their exact makeup and density convey different mechanical properties to the ECM in different tissue
    • repeating disaccharide unit
    • very versatile, can form gels that perform filtering functions (cartilage, vitreous humor, etc)
  12. Glycosaminoglycans (GAGs)
    • multiple GAGs can be linked to a single core protein to produce huge polymers of MW>106 D
    • prototypical GAG, hyaluronan
  13. Epithelial sheet stabilized attachment
    • epithelial cells rest on basal lamina composed of a special type of collagen (collagen IV) and laminin, which provides linking sites for cellular integrins
    • beneath the basal lamina, connective tissue composed of ECM collagen and proteoglycans provides a stabilized attachment surface
  14. Types of epithelial junctions
    • tight junction
    • adherens junction
    • desmosome
    • gap junctions
    • hemidesmosome
  15. Tight junctions
    • seals neighboring cells together in an epithelial sheet to prevent leakage of molecules between them
    • seal is incredibly tight and won't even admit small MW radioactive tracers from either the apical or the basal side.
  16. What are tight junctions formed of?
    occluding and claudin to stich up the two membranes of adjacent cells
  17. Adherens junctions
    • joins an actin bundle in one cell to a similar bundle in a neighboring cell
    • ties cells together through interactions with cadherins on adjacent cells that simply bind to each other tightly in the presence of Calcium. These cadherins are attached to cytoskeletal proteins through other linker proteins
  18. Desmosomes
    • joins intermediate filaments in one cell to those in another
    • cadherins in desmosomes are attached intracellularly to cytoplasmic plaques made of anchor proteins. Keratin filmaents within the cells are bound to the cytoplasmic plaques which create a linkage that can be drawn tightly together
  19. Hemidesmosomes
    • anchors intermediate filaments in a cell to the basal lamina
    • situation is analogous to desmosomes except integrins bridge the gap between the anchor proteins and the lamina
    • Kertain filaments still associate with the cytoplasmic plaque just like they do in desmosomes
  20. Gap junctions
    • forms channels that allow small water soluble molecules, including ions, to pass from cell to cell
    • provides avenues for transport between cells
    • in this case a tight seal is not wanted and instead channels are needed for cell to cell transfer of small analytes
    • these are provided by hexamer units called connexons
    • gap junctions are able to bridge the gap between cells by forming a dimer between two aligned connexons
  21. Skin organization
    • Layers of skin
    • Epidermis
    • loose connective tissues of dermis
    • dense connective tissue of dermis
    • fatty connective tissue of hypodermis
    • Another look at the skin layers, together with accessory cells (melanocytes, Langerhans cells) and connective tissues
  22. Plants outer organization
    • cellulose microfibrils are used in a manner analogous to collage, laid down in crossing layers. cellulose microfibrils have to be extruded extracellularly and so binding of the membrane to microtubule orients the fibers in one direction
    • cross-linking protein is pectin along with a glycan
    • everything between the outer plasma membrane and the middle lamella is the cell wall which allows turgor pressure to expand the cell perpendicular to the cellulose stacking
    • Plant cells are connected through plasmodesmata which are similar to gap junctions
  23. Stem cells
    • are called pluripotential stem cells
    • harvested from IVF embryos which have the potential to develop into any organ/tissue, etc.
    • once a cell is terminally differentiated, this ability is lost.
    • If the environment of the uterus can be replicated in vitro, these cells even have the potential to generate "fully functional" human clones
    • human embryos are currently stored in cryogenic freezers
    • completely solves the rejection problems in transplants
  24. Pluripotential stem cells
    • very early embryos in the blastocyst stage
    • blastocyst will just replaced harvested cells with new stem cells and develop normally if implanted.
    • can expand and freeze embryonic stem cells
  25. Three things that are needed for cell to be able to replace any cell type
    • 1) right signals
    • 2) environmental cutes
    • 3) at the right times during development
    • these three things aren't fully known yet, but advances are very rapid
  26. Hemopoietic stem cells in bone marrow
    • Bone marrow (hemopoietic) stem cells give rise to all blood cells, be they T or B, lymphocytes, polymorphonuclear leukocytes (PMNs), dendritic cells, platelets, RBCs, or cells of the monocyte/macrophage lineage (macrophages, osteoclasts)
    • Patients are irradiated to kill all rapidly dividing cells (basically lethal dose of radiation)
    • after the radiation treatment, patient is completely immunosuppressed. and donor bone is implanted and the donor stem cells populate the patient's bone marrow. If it is not a perfect match, patient has to take immunosuppressive drugs for life
  27. Oncogenes and tumor suppressor genes
    • dominant mutation (gain of function) - single mutation event in proto-oncogene creates a oncogene which activates mutation that enables the oncogene to stimulate cell survival and proliferation -> excess cell survival and proliferation
    • recessive mutation (loss of function) - mutation event inactivates tumor suppressor gene but no effect of mutation in one copy -> second mutation leads to two inactivating mutations functionally elimante the tumor suppressor gene which stimulates cell survival and proliferation -> excess cell survival and proliferation (cancer)
  28. Cancer metastasis
    • normal epithelium then tumor suppressor gene (APC) is lost -> excessive epithelial proliferation (oncogene RAS activated) -> small tumor then another tumor suppressor gene loss -> large tumor (third tumor suppressor gene p53 is lost) -> tumor becomes invasive which leads to rapid accumulation of mutations -> metastasis
    • Ras activation plus the loss of two tumor suppressor genes leads to uncontrollable cell division and metastasis
  29. Oncogenic kinase activated
    • oncogenic kinase is connected to ATP and a substrate
    • ATP then phosphorylates and ADP is released from the oncogenic kinase and the substrate is dissociated from the oncogenic Kinase along with the activated phosphate
    • the activated phosphate is the signal for cell proliferation and survival which then leads to leukemia
  30. Oncogenic Kinase blocked with Gleevec (chemotherapeutic drug)
    Gleevec takes place of ATP so when the substrate protein and oncogenic kinase dissociates the substrate does not have a phosphate on it that acts as a signal for cell proliferation -> no leukemia

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