Chapter 23

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  1. crystallins
    water soluble proteins; light focused on retina; as cells fill up with crystalline, cell is packed so densely, it stops functioning
  2. Which part of the body is the same as in the embryo?
    the lens

    It has the same protein; there is no turnover.
  3. Explain development of the lens.
    optical vessel starts to develop. Goes with ectoderm. Pinches off--> circularized and hollow---> identical cells
  4. What experiment can be utilized to see if replication is continuing/ occurring?
    pulse-chase analysis with BrdU
  5. Explin the structure of the retina.
    the region closest to the pigmented epithelium is where the color comes in 

    retina: cells (rods and cones) are permanent

    • When light stimulates the photoreceptors, the resulting electrical signal is relayed via interneurons to the ganglion cells, which then convey the signal to the brain. 
    • A population of specialized supporting cells occupies the spaces between the neurons and photoreceptors in teh neural retina
  6. What does the eye do?
    it dones't replace cells; it replaces proteins
  7. Explain rhodopsin-transducin
    • rhodopsin: is a G coupled protein receptor that has 7 transmembrane alpha helices; binds retinal, which is in the middle; a change in conformation leads to change of cis to trans retinal--> cascade of events
    • transducin: is the G-protein to which it is coupled;
    • It is a family of receptors that can receive signals in a variety of ways
  8. Explain the structure of a rod cell.
    It has discs of photoreceptive cells wwith photosensitive complexes; light absorbed here produces electrical response

    has an inner segment, nucleus, and synaptic region
  9. Explain the turnover of membrane protein in a rod cell.
    pigmented epithelial cell: recycles damaged proteins in cells of epthelium 

    followinga pulse of tritium-leucine, the passage of radiolabeled proteins through the cell is followed y autoradiograpy. The method revealed that tritium0leucine had been incorporated into proteins; the rest was washed out

    • 1) The incorporated leucine was first seen concentrated near the GOgli
    • 2) The, it passed to the base of hte otuer segment into a newly synthesized disc of photoreceptive membrane
    • 3-5) New discs are formed, displacing the older discs toward pigmented epithelium
  10. Explain the liver
    • a detoxifying organ; largest gland in body
    • 1) produces bile
    • 2) breaks downs toxins 
    • 3) stores (and regulates) glucose levels
  11. hepatocytes
    liver cells that are phenotypically rectangular in shape
  12. What is present in liver cells and what is its responsibility?
    fibroblasts are present and are responsible for production of ECM
  13. What do Kupffer cells do?
    they are macrophage-like adn deal with red blood cells
  14. fenestrated endothelial cells?
    capable of simple duplication
  15. What do mature liver cells do?
    they divide--> regeneration of liver (can happen several times)
  16. Hepatocytes in G0 phase has several molecules associated with it.
    1) urokinase-type plasminogen activator (aka: urokinase): produced by kidneys and circulates in teh bloodstream; helps produce a small amount of receptor that binds urokinase; chews apart ECM, digesting protein components of ECM

    2) hepatocyte growth factor produced by hepaotocytes in pro-factor growth form--> put out into ECM; gets bound in mature form and sits and waits for damage to occur

    3) c-Met receptor: receptor for activated hepatocyte growth factor can diffuse around membrane receptors bind and activate urokinase
  17. What is required if you have liver cells and an ECM?
    the connections the cells have with their external environment need to be in tact and mature
  18. Explain the urokinase activator?
    • 1) Chews apart ECM, digesting protein components of the ECM
    • 2) Cleaves peptide bond in hepatocyte growth factor
    • 3) mature; binds to c-Met receptor
    • 4) Signaling molecule causes re-entering of cell cycle
    • 5) response is proportional: more damage= greater response; more HGF activated, etc
  19. Differences between wound healing, regeneration, and cancer

    1) cell growth
    Wound healing: cell growth--> stop

    Reg: stop

    Cancer: doesn't stop
  20. Differences between wound healing, regeneration, and cancer

    2) Scar
    • WH: scar foms
    • rege: no scar
    • canc: tumor
  21. Differences between wound healing, regeneration, and cancer

    3) Cell types
    • WH: midrange (mid cells)
    • reg: multiple cell types grow back
    • cancer: fewer cell types
  22. Differences between wound healing, regeneration, and cancer

    4) Functionality
    WH: funcitonal in that you're not bleedng to death and other things but not completely functional

    • reg: functional tissue after regeneration
    • functional but not in an organismal way
  23. What is the lining of the gut?
    single layer of epithelium
  24. Crypts
    stem cells hidden away out of flow (upper region are TACs)
  25. villi
    absorption of nutrients and loss of cells
  26. What is the direction of movement?
    some move up and paneth cells move down
  27. Multipotent stem cells in livers do what?
    • give rise to 
    • 1) absorptive cells
    • 2) goblet cells: secrete mucus
    • 3) enteroendocrine cells: signaling between epidermis and dermis and go to brain
    • 4) Paneth cells: deal with bacteria that should not be there; secrete enzymes to destroy them
  28. How do they communicate inside adn outside of the cell?
    wnt pathway
  29. What is the original pathway that Wnt substitutes for?
    signal comes in, go amke TF we need; protein synthesized and modified---> find place where it needs to go

    This takes too much time
  30. Alternative
    alternative is the Wnt pathwa

    • make it all the time; when not needed, just destroy it. With Wnt signal, the destruction complex is broken up. No destruction--> Beta-catenin is free to diffuse and build up--> into nucleus (what used to repress= Goucho_
    • Beta catenin binds and causes gene expression

    Groucho co-represses cell proliferation genes
  31. Explain the Wnt pathway in detail.
    • 1) one of the Wnt proteins binds to the N-terminal extracellular cysteine-rich domain of a Frizzled family receptor (to faciliate Wnt signaling, coreceptors are required)
    • 2) Upon activation of the receptor, a signal is sent to the phosphoprotein Dishevelled, which is located in the cytoplasm
    • 3) Signal is transmitted via a direct interaction between Fz and Dsh, which are rpesent in all organisms
  32. Explain Frizzled.
    spans the plasma membrane seven times and constitue a distinct family of G-protein coupled receptors
  33. What is the Wnt pathway in liver?
    pathway that causes an accumulation of beta-catenin in teh cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of TFs 

    Without Wnt signaling, the Beta-catenin won't accumulate since a destruction complex would normally degrade it, which includes APC, and others. Beta-catenin is ubiquitlyated and sent to a proteasome.

    However, when Wnt binds Frazzled, the destruction complex function becomes disrupted. This is due to Wnt causing the translocation of the negative Wnt regulator, Axin, and the destruciton complex to teh membrane.
  34. What happens when you knock out or Cre-lox Wnt?
    no Wnt= no proliferation
  35. What happens when you knock out or Cre-lox APC?
    overproduction of the system due to an inability to Ub something
  36. What else does Wnt do?
    • we need to develop multiple cell types in correct proportions
    • One way this happens is with Notch, a receptor protein in the membrane of certainc ells

    It binds to Delta ligand on the surface of other cells--> contact--> info transmitted to nucleus of cells--> grow up differently based on identity
  37. How do Wnt and Notch combine.
    Wnt signaling maintains proliferation in teh crypt, where the stem cell resides and tehir progeny become committed to different fates

    Wnt signaling int he crpty drives expression ofthe components of the Notch signaling pathway in that region; Notch signaling is thus active in the crypt, and through lateral inhibition, forces cells there to diversify. Both pathways must be activated in the same cell to keep it as a stem cell. The progeny of the stem cell continue dividing under the influence of Wnt even after commitment to a specific differentiated fate
  38. How do you know when the time to differentiate is now?

    Also, what is an experiment that occurred?
    • Wnt and Notch affect other cell processes
    • If in crypt, you have EphB

    As you mgirate further, you stop producing EphB and start producing ephrinB

    Experiment of these proteins regulated by Wnt signal which diffuses out of epidermis, causing cells to produce BMP4, received by cells in villus and causing maintenance of differentiatd state
  39. Wnt detained again
    • In the absence of Wnt, cytoplasmic β-catenin protein is constantly degraded by the action of the complex consisting of APC (APC), casein kinase 1 (CK1), and glycogen synthase kinase 3 (GSK3).
    • When Beta-catenin is not required for activity in the cell, it is going to be ubiquitylated to eliminate it and thus prevent Beta-catenin from reaching the nucleusà Wnt target genes are thereby repressed
    • The Wnt/β-catenin pathway is activated when a Wnt ligand binds to a seven-pass transmembrane Frizzled (Fz) receptor and its co-receptor, (LRP6) or its close relative LRP5.
    • This results in the recruitment of the scaffolding protein Dishevelled (Dvl), which phosphorylates and deactivates the complex of APC, CK1, and GSK3.  
    • Beta-catenin is stabilized, allowed to travel to the nucleus, and thus activate Wnt target gene expression
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Chapter 23
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