Cell-Cell Interaction (Part 1: Cell Junctions)

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"Of all the social interactions between cells in a multicellular organism, the most fundamental are those that hold the cells together”

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Cell-Cell Interaction (Part 1: Cell Junctions)

  1. 1. INTERNET WORLD http://en.wikipedia.org/wiki/File: Internet_map_1024.jpg
  2. 2. Tree of Life !!!
  3. 3. “ Whole being greater than the sum of individual parts”
  4. 4. Cell-Cell Interactions Cell Signals one another with chemicals (Cell Signalling) Integration of cells into tissues : Cell surface Proteins Mediates Cell-Cell Interactions Expression of Cell Identity Cell-Cell Adhesion- CAMs Cell-matrix adhesion CAMs and ECM can bind cell together, and transfer of information between the exterior and interior cells.
  5. 5. Different types have different Functions cellular coat Protection- water loss and wear & tear Seal surfaces Cell junctions key to formation Mechanical flow of materials Regulatestresses-transmittedof epithelial and maintenance by cytoskeletal filaments –anchored to cell-matrix & cell-cell adhesion sheets Extracellular matrix directly bears mechanical stresses Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H Freeman)
  6. 6. Major Adhesive Interactions Molecular Biology of the Cell (2008, Garland Publishing)
  7. 7. Major Adhesive Interactions Molecular Cell Biology (2004, W H Freeman)
  8. 8. Major Adhesive Interactions Molecular Biology of the Cell (2008, Garland Publishing)
  9. 9. ……………. Adhesive Interactions Molecular Cell Biology (2004, W H Freeman)
  10. 10. Transmembrane Adhesion Proteins Molecular Biology of the Cell (2008, Garland Publishing)
  11. 11. Cell Adhesion Molecules (CAMs) Don’t bind each other Ca2+ independent Molecular Cell Biology (2004, W H Freeman)
  12. 12. Cell Adhesion Molecules (CAMs)
  13. 13. Cadherins- Classical Vs Non-Classical Name Main Location Classical (are major components of cell-cell adhesion) E- Cadherin Expressed on early embryonic cells in mammals. Later becomes restricted to embryonic and adult epithelial tissue N- Cadherin First mesodermal, later CNS (Neurons, heart, skeletal m., kens and fibroblast) P- Cadherin Trophoblast cells (Placenta), epidermis, breast epithelium VE- Cadherin Endothelial cells
  14. 14. Non-Classical Cadherins Desmocollin Skin Desmoglein Skin T-Cadherin Neurons, muscle and Heart Cadherin-23 Inner year, other epithelia Desmosomal Lacks a transmembrane domain Fat (Drosophila) Epithelia and CNS Fat-1 (Mammals) Epithelia and CNS α, β and γProtocadherins a Seven-Pass Transmembrane Cadherin Flamingo Neurons Sensory & some other epithelia
  15. 15. Cadherins and Cell-Cell Adhesion The C-terminal cytoplasmic domain associates with cytoskeleton The N-terminal extracellular domains form dimer and through homoplilic interactions, form tetramers Molecular Biology of the Cell (2008, Garland Publishing)
  16. 16. Cadherins and Cell-Cell Adhesion The cells segregate according to the cadherins they express Molecular Biology of the Cell (2008, Garland Publishing)
  17. 17. Cadherins and Cell-Cell Adhesion Cadherin-dependent cell sorting Molecular Biology of the Cell (2008, Garland Publishing)
  18. 18. Compaction of an Early Mouse Embryo At eight-cell stage, begin to express E -cadherin Molecular Biology of the Cell (2008, Garland Publishing)
  19. 19. Cadherins mediate Ca2+ -dependent homophilic cell-cell adhesion Extracellular domains of a classical cadherin (C-cadherin) Molecular Biology of the Cell (2008, Garland Publishing)
  20. 20. Cadherins mediate Ca2+ -dependent homophilic cell-cell adhesion  Ca binds in the hinge regions between cadherin domains, and prevent the flexing.  Without Ca the molecule is floppy and adhesion fails Molecular Biology of the Cell (2008, Garland Publishing)
  21. 21. Hook and Loop Fasteners Velcro !!!
  22. 22. Many cadherin molecules are in a junction, functioning like a Velcro. Molecular Biology of the Cell (2008, Garland Publishing)
  23. 23. Epithelial-mesenchymal transition In mesenchymal cells the adhesion molecules are switched off. The transition is regulated by gene regulatory components named Slug, Snal and Twist. They affect E-cadherin expression Twist suppresses E-cadherin. It is involved in malignant transformation.
  24. 24. Linkage of classical cadherin to actin filaments Molecular Biology of the Cell (2008, Garland Publishing)
  25. 25. Protein constituents of typical adherens junction Molecular Cell Biology (2004, W H Freeman)
  26. 26. Desmosome Anchor Proteins Molecular Biology of the Cell (2008, Garland Publishing)
  27. 27. Molecular Biology of the Cell (2008, Garland Publishing)
  28. 28. Cell-cell junctions signalling Level of p120-catenin regulates cell junctions Beta-catenin - wnt-signalling Flamingo - as a GPCR VE-cadherin - for response to VEGF
  29. 29. Selectins mediate cell-cell adhesion in the bloodstream bind carbohydrates (lectins) Molecular Biology of the Cell (2008, Garland Publishing)
  30. 30. Leucocyte- endothelial cells interactions Molecular Biology of the Cell (2008, Garland Publishing)
  31. 31. Molecular Cell Biology (2004, W H Freeman)
  32. 32. Immunoglobulin superfamily The Ig-superfamily members mediate Ca-independent cell adhesion. ICAM and VCAM (Cellular Adhesion Molecules) bind integrins Other types may have homophilic binding Molecular Biology of the Cell (2008, Garland Publishing)
  33. 33. Integrins: cluster into adhesive strs. In nonepithelial cells Molecular Biology of the Cell (2008, Garland Publishing)
  34. 34. Molecular Biology of the Cell (2008, Garland Publishing)
  35. 35. Molecular Cell Biology (2004, W H Freeman)
  36. 36. Molecular Cell Biology (2004, W H Freeman)
  37. 37. Fibronectin binding to Integrin Molecular Cell Biology (2004, W H Freeman)
  38. 38. Tight Junctions Molecular Cell Biology (2004, W H Freeman)
  39. 39. Gap Junctions Molecular Biology of the Cell (2008, Garland Publishing)
  40. 40. Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H Freeman)
  41. 41. Summary Molecular Biology of the Cell (2008, Garland Publishing)
  42. 42. More Reading……….. ECM of Epithelial Sheets- basal lamina, collagen, laminin, proteoglycans ECM of Nonepithelial Tissues- fibrillar collagens, association of hyaluronan and proteoglycans, fibronectins Plasmodesmata Cell Signalling
  43. 43. “ Were the various types of cells to lose their stickiness for one another and for the supporting extracellular matrix, our bodies would at once disintegrate and flow off into the ground in a mixed stream of cells.” Warren Lewis (1922)

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