Epithelial Tissue Contain Multiple Types of Cellular Junctions

1
Epithelial Tissue Contain Multiple Types of
Cellular Junctions
15-23
2
There are five principal classes of
cell-adhesion molecules (CAMs)
Extra Cellular Matrix
Figure 22-2
3
Cell-Cell Adherens/Anchoring Junctions often
seen as continuous belt that surrounds the cells
(zona adherens). This belt is located at the apex
of the cell usually just below a tight junction
Juxatposed cadherins form the adherens junction
18-35
4
Cadherin-containing junctions connect cells to
one another and are linked to either the actin or
IF cytoskeleton
?,b,?, catenins
Figure 22-5
5
Cadherins Mediate Most Ca-dependent Adhesion.
Cadherins have multiple extracellular Ca-binding
Domains In addition they have one or more
highly non-conserved domains on their
extracellular surface through which they mediate
homophilic interactions
The Basic Structure of Cadherins
Extra Cellular Matrix
IntraCellular Catenin Complexes (a, b, g,
/vinculin/a-actinin/plakoglobin) Anchor Cadherins
to Cytoskeletonal Actin (adherens) or Keratin
(Desmosomes)
Figure 22-2
6
Cadherins mediate Ca2-dependent homophilic
cell-cell adhesion
(placenta)
7
Cadherin Expts in L-Cell Fibroblasts

• Demonstrate Ca2 dependency
• homophilic interactions
• Ability to sort based on Cadherin type
  Expression levels

8
N-cams Mediate Ca2-Independent Homophilic
Cell-cell Adhesion
Extra Cellular Matrix
Figure 22-2
9
N-CAMs mediate Ca2-independent homophilic
cell-cell adhesion
Negative charge on Sialic Acid is important for
repulsion
Figure 22-3
10
Desmosomes intercellular rivets
Figure 22-6
11
Gap junctions are Links for Intercellular
Communication by allowing small molecules to pass
between adjacent cells
Figure 22-7
12
Connexin, a Transmembrane Protein, Forms
Connexons That Link to Create Cylindrical
Channels in Gap Junctions
1 Gap Junction 2 Connexons 1 Connexon 6
Connexin Proteins 1 Connexin Protein 4 TM
Domains
MW Cutoff for GJs is 1200Daltons (Ca2, cAMP,
electrical coupling) GJs are GATED Closed by
cytosolic high Ca2/ low pH
Figure 22-8
13
Integrins are the Major Class of Cell Surface
Receptors for the Extracellular Matrix
Heterodimeric Protein Complex with low ECM
affinity but High Concentration leading to
thethe velcro effect Non-covalently linked a/b
subunits lead to much tissue specific
diversity with many many isoforms. Both
subunits contribute to binding with diverse ECM
interactions Ca2/Mg2 Dependent Interact with
actin or keratin (hemi-desmosomes) through
intracellular attachment proteins
(talin/a-actinin) that associate with the
cytoplasmic tail of b-subunit.
Extra Cellular Matrix
Figure 22-2
14
Integrins Are TM Heterodimers (ab Combinations)
That Mediate Weak Cell-Matrix and Cell-Cell
Interactions
Cell-matrix adhesion is modulated by changes in
the activity and number of integrins De-Adhesion
factors promote cell migration and can remodel
the cell surface
15
Integrin-Containing Junctions Interact With Both
Actin and IF Cytoskeleton to Connect Cells to the
Substratum of the ECM
Integrins are dynamic adhesion molecules that can
regulate their ECM binding
Figure 22-9
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De-Adhesion Factors
When the mobilization of cells is very important,
rapid DeAttachment from the ECM can be
accomplished thru the destablization of Integrin
mediated attachment
DISINTEGRINS are small peptides rich in RGD
repeats that are the integrin binding site that
are also enriched in many ECM proteins (eg
fibronectin). Other De-Adhesion factors are
basically proteases that degrade ECM
components fibrinogen (attacks
fibronectin) matrix-specific metalloproteinases
(MMPs) ADAM (A Disintegrin And a
Metalloproteinase) is a family of membrane
anchored glycoproteins that has both domains
17
The Extra-Cellular Matrix (ECM)

• Fills the void of extracellular space
• Made up of locally secreted network of proteins
  and polysaccarides
• that remain associated with the cells that
  synthesized them.
• Great variation from rock hard (bones, teeth) to
  transparent (cornea)
• Basal Lamina is mat-like substratum for epithelia

Composed of 2 main Classes of Macromolecules Fibro
us proteins Structural collagen/
elastin Multi-Adhesive fibronectin/
laminin Polysaccaride Glycosaminoglycans Proteogl
ycans
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Collagen The Fibrous Proteins of the Matrix
Collagens constitute the most abundant class of
animal proteins-25 of total Mass!!
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The basic structural unit of collagen is a triple
helix
Fibrils stabilized by novel Collagen and elastin
Pro/Lys X-links that are specific for these
proteins
Collagen fibrils form by lateral interactions of
triple helices
Figure 22-11
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The side-by-side interactions of collagen helices
are stabilized by covalent bonds
Figure 22-12
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Collagens form diverse structures
Figure 22-16
Types VI and IX are Fibril-Associated Collagens
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Assembly of collagen fibers begins in the ER and
is completed outside the cell
Hydroxylation of Pro Lys glycoslyation of Lys
Cleavage of C and N terminal propeptides makes
collagen 1000x less soluble Impt this occurs
OUTSIDE of cell
Figure 22-14
23
Mutations in collagen reveal aspects of its
structure and biosynthesis as well as
thepathological basis for SCURVY
Figure 22-15
Vit. C is required cofactor for the prolyl
oxidase enzyme that carries out the hydroxylation
of proline. Without this modification collagen is
much less stable and skin and tendon are fragile
and defective
24
Type IV collagen forms a network in the basal
lamina
Figure 22-17
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Laminin and type IV collagen form the
two-dimensional basal lamina
Figure 22-18
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Structure of Laminin Trimer (850 kD total MW)
Figure 22-19
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Model of the basal laminaconsists of LAMININ,
type IV COLLAGEN, the proteoglycan PERLECAN, and
ENTACTIN (a multiadhesive protein)
Figure 22-20
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The basal lamina is structured differently in
different tissues
Figure 22-21
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Fibronectins non-collagen adhesion proteins
that bind many cells to fibrous collagens and
other matrix components
2 large subunits linked by S-S bonds, each
subunit with multiple rod-like domains seperated
by flexible spacers. Major player is Type III
domain that binds Integrins on the cell surface
-VERY RICH IN RGD (ARG, GLY, ASP) REPEATS
Figure 22-22
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Proteoglycans consist of multiple
glycosaminoglycans linked to a core protein
Glycosaminoglycan structures
Figure 22-24
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Glycosaminoglycan chains in proteoglycans
Initial tetra-saccaride modification
Figure 22-25
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Extracellular matrix proteoglycans
Hyaluronan resists compression and facilitates
cell migration
Figure 22-26
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Cell-surface proteoglycans-The Syndecan Family of
Single TM proteins
Figure 22-27
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Many growth factors are sequestered and presented
to cells by proteoglycans
Figure 22-28