CFM2: Cell Adhesion

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  1. Ig-CAMs
    • Immunoglobulin-like cell adhesion molecules
    • Transient and dynamic neural and lymphocye interactions
    • Homophilic and heterophilic interactions
  2. ______ can be subverted as viral receptors
    Ig-CAMs (ex: I-CAM for rhinovirus)
  3. 5 classes of CAMs
    • Ig-CAMs
    • Proteoglycans
    • Selectins
    • Integrins
    • Cadherins
  4. Calcium-independent CAMs
    • Ig-CAMs
    • Proteoglycans
  5. Calcium-dependent CAMs
    • Selectins
    • Integrins
    • Cadherins
  6. Proteoglycans
    • Calcium-independent cell adhesion molecule that binds cells to ECM
    • Has glycerin side chains that sequester growth factors
  7. Selectins
    • Calcium-dependent cell adhesion molecule
    • Bind sugars via lectin domain (greater specificity allowed with sugars)
    • Involved in lymphocyte homing by means of vascular addressins
  8. Vascular addressins
    Extracellular endothelial proteins that bind to lymphocyte selectins, allowing lymphocytes to "roll" along and patrol endothelial linings of blood vessels.
  9. Integrins
    • Calcium-dependent cell adhesion molecules; complex family of a- and b-subunits
    • Bind divalent cations, like calcium and magnesium
    • A few bind Ig-CAMs, cadherins, clotting factors
    • Most connect ECM to cytoskeleton at focal contacts and hemidesmosomes
    • Potentiate growth and survival signals
  10. Cadherins
    • Mediates cell-cell adhesion in adherens junctions and desmosomes
    • Initiates cell adhesion
    • Beta-barrel structure
    • C-terminal cytoplasmic domain: highly conserved
    • Extracellular ectodomain: 5 repeats of ~110 aa's with negatively charged amino acids that bind calcium
  11. Cadherin dimers
    • Calcium binds to and rigidifies cadherin repeats
    • Cis dimers between cadherins on same cell
    • Trans dimers formed with cadherins on neighboring cells
  12. Puncta adherens
    Small points of filopodial contact where cadherins can initiate cell-cell adhesion
  13. Adherens junction structure
    Image Upload 1
  14. p120
    • In adherens junction
    • Functions to prevent internalization of E-cadherin
  15. _______ initiate cell adhesion and change the shape of the cell
    Adherens junctions
  16. Loss of E-cadherin
    Plays a role in breast cancer metastasis
  17. Loss of alpha catenin
    Plays a role in cancer metastasis (loss of cell adhesion)
  18. Wnt, APC, and beta catenin
    • Wnt inhibits APC, which inhibits beta┬ácatenin
    • Active Wnt leads to less APC leads to more beta catenin, leads to more transcription, leads to cancer
  19. Adherents junctions bind ______; desomosomes bind _______ (microtubules, actin filaments, intermediate filaments)
    Actin filaments; intermediate filaments
  20. Intracellular region in desmosomes is (wider/narrower) than that in adherens junctions
  21. Structure of desmosome
    Image Upload 2
  22. Desmosome cadherins
    • Desmoglein
    • Desmocollin
  23. Desmosome catenins
    • Plakoglobin
    • Plakophilin
  24. Adherens junction:E-cadherin::Desmosome:?
  25. Adherens junction:b-catenin::desmosome:?
  26. Adherens junction:p-120::desmosome:?
  27. Adherens junction:a-catenin::desmosome:?
  28. Pemphigus vulgaris
    Autoimmune disorder where patients have antibodies against desmoglein 3
  29. Pemphigus foliaceus
    Autoimmune disorder where patients have antibodies against desmoglein 1
  30. Staph a. toxins and bullous impetigo toxins target _______
    desmoglein 1
  31. Naxos Disease
    • Mutation in plakoglobin so it can't bind to desmoplakin
    • Woolly hair, palmoplantar keratoderma, and arrhythmogenic right ventricular cardiomyopathy
  32. Carvajal Syndrome
    • Mutation in desmoplakin
    • Woolly hair, palmoplantar keratoderma, arrhythmogenic right ventricular cardiomyopathy
  33. Arrhythmogenic Cardiomyopathy
    • Often caused by mutations in desmosomal proteins
    • Bad cell adhesion due to lack of desmosomal proteins leads to bad gap junctions leads to arrhythmia
  34. Ectodermal Dysplasia - mutation in ______
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CFM2: Cell Adhesion
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