Cell Adhesion

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Cell Adhesion

• 311 304 Cell Molecular Biology
• September 1, 2006
• Lecturer Mr. Jirapat Chunthapong

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Introduction
Cross-sectional view of part of the wall of the
intestine
Alberts et al., 2002
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Polarized epithelial cells have distinct apical,
basal, and lateral surfaces
Lodish et al., 2004
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1. Cell Adhesion Molecules
Lodish et al., 2004
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2. Cell Junctions

• Three major classes of cell junctions
• Anchoring junctions
• Tight junctions
• Gap junctions

Lodish et al., 2004
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A summary of various cell junctions found in
vertebrate epithelial cells
Alberts et al., 2002
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2.1 Anchoring Junctions

• Specialized region on the cell surface
• Contains cell-adhesion molecules or adhesion
  receptors that interact with other cells or the
  extracellular matrix and with cytoskeletal fibers
• Major types
• Adherens junctions (zonula adherens)
• Desmosomes (macula adherens)
• Hemidesmosomes

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2.1.1 Adherens Junctions

• Also known as zonula adherens
• A type of specialized adhesive junction,
  partially common in epithelia
• Plasma membranes of adjacent cells are connected
  by cadherins or other cell adhesion molecules
  (e.g., integrins)

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Alberts et al., 2002
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Lodish et al., 2004
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The influence of extracellular Ca2 on structure
and function of E-cadherin
Alberts et al., 2002
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Lodish et al., 2004
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Alberts et al., 2002
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2.1.2 Desmosome

• Also known as macula adherens
• Disc-shaped adhesive junction (1 mm diameter)
• Located basal to adherens junction
• Contains desmogleins desmocollins (desmosomal
  cadherins structurally different from classical
  cadherins)
• Found in variety of tissues (esp., those that
  need mechanical strength e.g., cardiac muscle
  epithelia of skin and uterine cervix)

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(No Transcript)
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• Dense cytoplasmic plaques, on the inner surface
  of plasma membrane, contains desmoplakins
  plakoglobin
• Serves as site of anchorage for looping
  intermediate filaments that extend into the
  cytoplasm

Schematic model showing components of a desmosome
Lodish et al., 2004
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• Desmoplakins plakoglobin serve as adaptor
  proteins that link desmosomal cadherins to
  intermediate filaments
• 3-D network of intermediate filaments provides
  structural continuity and tensile strength to the
  entire sheet of cells
• Pemphigus vulgaris (an autoimmune disease) has
  antibody against one of his/her own desmogleins ?
  loss of epidermal cell-cell adhesion ? severe
  blistering of the skin

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2.1.3 Hemidesmosome

• Specialized adhesive structure at the basal
  surface of epithelial cells
• Function attach the cells to their underlying
  basement membrane (basal lamina)
• Contains a dense plaque on the inner membrane,
  with keratin-containing intermediate filaments
  coursing out into the cytoplasm

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Lodish et al., 2004
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a b
Karp, G., 2005
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A hemidesmosome junction
Nature Reviews Genetics 3, 199-209 (2002)
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2.2 Tight Junctions

• Seals adjacent epithelial cells together
• Locate at the very apical end of junctional
  complexes between cells
• Form a selective permeability barrier across
  epithelial sheet
• Seals off body cavities such as intestine,
  stomach lumen, bile duct, blood-brain barrier,
  etc.

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Lodish et al., 2004
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(a)
(b)
(c)
Tight junctions (a) From freeze-fracture
preparation, (b) Schematic diagram,
(c) Major proteins of tight
junctions
Lodish et al., 2004
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• Freeze-fracture preparation reveals the structure
  of tight junction as a honeycomb-like network of
  ridges grooves
• Linkage of rows of protein particles (3-4 nm Ø)
• Major proteins occludin, claudin-1, JAM
  (junction adhesion molecule)
• Prevents the diffusion of macromolecules across
  epithelial sheet
• Prevents diffusion of membrane proteins and
  glycolipids between the apical and the
  basolateral regions of the plasma membrane

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Transcellular and paracellular pathways of
transportIn paracellular transport, molecules
move through tight junctionswhose permeability
to small molecules and ions depends on the
composition of the junctional components and the
physiologicalstate of the epithelial cells
Lodish et al., 2004
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Alberts et al., 2002
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The role of tight junctions in allowing epithelia
to serve as barriers to solute diffusion
Alberts et al., 2002
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2.3 Gap Junctions

• Sites between animal cells that are specialized
  for intercellular communication
• Span the adjacent plasma membranes with very fine
  strands or molecular pipelines that allow the
  passage of small molecules (1000 daltons)
• Electrical metabolic couplings

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Lodish et al., 2004
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Alberts et al., 2002
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• Gap junctions are constructed from transmembrane
  protein called connexin
• Six identical protein subunits assemble to form a
  structure called connexon
• Two connexons from adjacent plasma membranes
  align to form a continuous aqueous channel of gap
  junction
• Gap junctions in different tissues can have
  different permeability due to difference in
  connexin (there are at least 11 distinct
  connexins)