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Lecture The cell concept (PowerPoint)

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					    Lecture 26: Extracellular matrix

                  May 4, 2005
        Today’s lecture: Karp Chapter 7
     Mallard quiz 11 – due Tues., May 10, 3:59 pm
        Final exam – Wed., May 11, 3:10 p.m.
 Review session – Tues., May 10, 7:30 --? Mlt 208
      Final exam will cover lectures 20 – 26;
See Karp chapters 12 (pp494-500), 7, 8 and 9.
          Adhesive proteins in the ECM
• Two major adhesive proteins
   – Laminin
   – Fibronectin
• Large proteins with multiple binding sites for:
   –   GAG units (e.g. heparin)
   –   Collagen
   –   Cell receptors (integrins)
   –   Fibrin (from fibrinogen – converted by thrombin to
       create clots.)
• The proteins help anchor ECM to PM of the cell
                      Fibronectin (FN)
•   Glycoprotein: 5% CHO
•   Dimer: each subunit has 2500 a.a.
•   Multiple binding domains
•   FN in blood and in ECM
    – Fibrin domains: binds to blood clots and platelets
                       Laminin
• Large
  heterotrimer
  – 850,000 MW
  – cross shaped
• Multiple binding
  domains
  – Type IV collagen
  – Heparin sulfate
  – Integrins
• Found in basal
  lamina
     Cell attachment in vitro
• Cells adhere poorly to glass
  substrates
   – FN increases attachment
   – Allows movement
• Cells adhere better to plastic
   – Many tumor cells don’t stick
   – Correlated w/ metastatic potential
• FN in vivo:
   – Movement during development
   – Wound healing



                                          Cell adhesion over time
                Basement membrane
• Found around muscle cells, fat cells, Schwann
  cells.
• Continuous, thin, tough sheets containing
  –   Type IV collagen
  –   Proteoglycans
  –   Laminin
  –   Other proteins (i.e. entactin)
  –   Under epithelial cells
• FN: binds basement membrane to connective
  tissue
Basal Lamina
                           Integrins
• Dimeric
   – 100-150 kd MW
   – Low affinity ~ 106 to 108
   – High number (FN
     receptor = 500,000/cell)
   – Both subunits needed
• Multiple subunits
   – 18  and 8  subunits
   – 20+ different types of
     integrins
Cell binding domain
of adhesive proteins
• Tripeptide RGD
   – Arg-Gly-Asp
   – RGD protrudes from
     protein structure
• Found in other proteins
   –   Laminin
   –   Fibronectin
   –   Proteoglycans
   –   Collagen
• RGD peptide competes
  with FN
Integrins mediate transmembrane interactions
                   to ECM
 Fibronectin structure
Hemidesmosomes link cells to the ECM
           How cells interact: cell junctions

• Hemidesmosomes
   – Connection to ECM
• Tight junctions
   – Barrier to diffusion
• Adherns junctions
   – Zipper-like:
• Desmosomes
   – Spot welds between cells
• Gap junctions
   – Small channels between cells
Tight junctions – continuous belts around cells
         Cells lining body cavities
         Capillaries in brain and testis
         (blood/brain barrier)




Note: plasma membranes partially fuse.
Stop movement across epithelium.
    Divide PM into two regions (apical
    and
        basal lateral)
        Adherens junctions (Zona adherens)

• Organize microfilaments
• Formed by interaction of
  cadherin proteins
   – Homotypic interactions
     (same cadherin on both
     cells)
   – Ca++ dependent
   – Interact with proteins in
     opposite cell
   – In epithelial cells, form a
     belt under tight junction.
Adhesion belts  complex structures
         Desmosomes link cells
via cadherins and intermediate filaments
                    Gap Junctions
• Direct communication between neighboring cells
   – Electric coupling, also ions, small molecules <1000 MW
   – Can be rapidly closed; sensitive to Ca++
   – Connexins: 4-6 subunits form junction cylinder.
    Tissues contain different cell types
(gut has cells for absorption and secretion)
  Tissues: cells in the more complex structures


Goblet and absorptive cells
Stem cells and the formation of tissues

                         Undifferentiated
Tissue renewal in the gut
Tissue renewal in the skin
Cell types in the blood
Origin of blood cell types

				
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