ECM: Continued

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Chapter 11

• ECM Continued

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Glycocalyx

• Carbohydrates on cell surface of animal cells
  external to plasma membrane
• Functions
• Recognition
• Adhesion
• Protection of cell surface
• Creation of permeability barriers

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2 Types of Glycocalyx

• Attached glycocalyx inherent in cell surface
  cant remove without removing plasma membrane
• Carbohydrates attached to glycoproteins and
  glycolipids
• Unattached glycocalyx material is external to
  membrane that can be removed without disrupting
  cell
• Glycoproteins and proteoglycans usually hard to
  separate from the ECM

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Cell-Cell Recognition and Adhesion

• Associate in precise patterns to form tissues
• Require recognition, adherence and communication
  with each other
• Adhesion receptors serve to bind cells to one
  another

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Transmembrane Proteins

• Immunoglobulin superfamily
• Cadherins
• Selectins
• Few integrins (usually links cell to ECM by
  linker proteins)
• Receptor on cell 1 binds ligand on cell 2 may
  or may not be identical
• Homophilic interactions same ligands CAMS
• Heterophilic interactions binds different
  molecules - selectins

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CAMS

• Cell Adhesion Molecules
• Members of the Ig-superfamily (IgSF)
• Have loops that bind CAMs on adjacent cells
  together
• Homophilic and Ca-independent
• N (neural)-CAM first identified without it
  there was no organized neural tissue
• LI-CAM important in neural development

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Cadherins

• Adhesive glycoproteins in plasma membrane
• Important in cell recognition and adhesion
• Requires Ca for function
• Have subunits in the extracellular domain that
  vary in number of repeats
• E-cadherin has 5 subunits, act in pairs in the
  cell membrane homophilic- like a zipper

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Cadherin Binding
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3 Types of Cadherins

• Connect to the cytoskeleton
• 3 types each is in different cell types and
  appear at different embryonic stages
• Helps to segregate cells into specific tissues
  interfere with cadherins will result in embryo
  failing to organize
• E-cadherin epithelial tissues
• P-cadherin placental tissues
• N-cadherin nervous tissues
• Expression change in cancer loose them and the
  cancer breaks up and migrates to other location -
  metastasis

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Carbohydrate Side Chains

• CAMs and cadherins has long oligosaccharide side
  chains
• N-CAM has sialic acid negative charge
• Amounts change during development
• ??? regulation

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Lectins

• Secreted carbohydrate binding proteins
• Cell-cell adhesion binds sugars or specific
  sugar on the surface
• Can bind at 2 sites linking 2 cells together
• Important on RBC
• Regulates their survival loose sialic acid and
  then targeted for removal
• Different sugars on the cell surface that is
  recognized by antibodies in the blood

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Blood Types and Sugars

• Antigens on surface of RBS
• Type A GalNAc
• Type B Gal
• Type AB Gal and GalNAc
• Type O - none

• Antibodies in the serum
• Type A has Ab to Gal (anti-B Ab)
• Type B has Ab to GalNAc (anti-A Ab)
• Type AB has none
• Type O has Ab to both Gal and GalNAc (anti-A and
  anti-B Ab)

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Selectins and Leukocyte Adhesion

• Selectins are glycoproteins on cell surface of
  endothelial cells in blood vessels
• L-selectin leukocytes
• E-selectin endothelial cells
• P-selectin endothelial cells and platelets

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Extravasation

• WBC roll on endothelial lining of the blood
  vessel
• When inflammation P- and E-selectin expressed on
  endothelial cells
• WBC binds and then binds to integrin and ICAM
  (heterophilic) and moves out of the blood vessel

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Cell Junctions

• Long term association
• Modification of plasma membrane at point where
  cells meet Cell Junction
• Adhesive junctions
• Tight junctions
• Gap junctions
• Plant cells have plasmadesmata because of cell
  wall prevents plasma membrane from forming above
  structures

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Cell Junctions
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Adhesive Junctions

• Also called anchoring junctions
• Link cells together to make tissues
• All junctions link cytoskeleton of one cell to
  the cytoskeleton of adjacent cell or to the ECM
• Gives tissues integrity and ability to withstand
  mechanical stress
• Many in the heart muscle and skin epithelium

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Cell-Cell Adhesive Junction

• Adherens junction attach to microfilaments
• Desmosomes- attach to intermediate filaments,
  intracellular attachment proteins form a fibrous
  plaque
• 2 distinct proteins
• Intracellular attachment protein link junction
  to appropriate cytoskeleton filament on the
  inside of plasma membrane
• Cadherins protrude on outer surface of membrane
  and bind cells together or to ECM

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Adherens Junction

• Cadherin-mediated junction connect by actin
  microfilaments
• Prevalent in heart tissue and tissues that lines
  body cavities and organs
• Epithelial tissues forms adhesion belt points
  of attachment between cell surface and
  cytoskeleton
• Connected by linker proteins ? and ? catenin
• ? catenin connects to cytoplasmic tail of
  cadherin
• ? catenin binds to ? catenin to actin

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Adhesion Junction
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Desmosomes

• Buttonlike points of string adhesions between
  adjacent cells
• Structural integrity functions as a unit to
  resist stress
• Abundant in the skin, heart and neck of uterus

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Desmosomes
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Desmosome Structure

• Membrane is adjacent space is the desomsome
  filled with desmocollins and desmogleins
• Both are cadherins that interact with plaque on
  inner surface and mediate cell-cell attachments
  at outer surface
• Plaque is just below plasma membrane
• Made up of desmoplakin and plakoglobin (? catenin
  family)
• Desmoplakin attaches to tonofilaments that are
  intermediate filaments vimentin, desmin or
  keratin anchors in cytoplasm
• Links intermediate filaments in adjacent cells,
  continuous cytoskeletal network

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Tight Junction

• No space between adjacent membranes
• Acts as seal prevent flow of fluids between
  cells cant pass from 1 side of cell layer to the
  other between cells need to go thru cell by way
  of membrane
• Abundant in intestinal epithelial cells, ducts
  and cavities of organs liver, pancreas and
  bladder

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Tight Junction

• Not entire area of contact forms a series of
  ridges
• Major protein claudin and occludin
• Claudin is more important large family
  different ones expressed in different cells types
• Number of ridges corresponds to tightness of
  junction

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Tight Junction Function

• Block lateral movement of membrane proteins and
  lipids
• Integral are completely blocked
• Lipids are blocked in outer leaflet
• Sets up a polarity of cells discrete functional
  groups at opposite ends of cell
• Basal surface
• Apical surface

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Movement of Glucose
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Gap Junctions

• Point of contact between 2 adjacent cells
• Can move ions and small molecules across
  electrical and chemical communication
• Joined by tightly packed, hollow cylinders called
  connexons 1 to 1000s of connexons
• Each has 6 subunits of connexin many different
  types found in different cells
• Invertebrates have innexins
• Abundant in cells that need rapid communication
  between cells

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Tight Junction