1. CELL ADHESION
MOLECULES
Department of Natural Sciences
University of St. La Salle
Bacolod City

2. Major families of cell-adhesion molecules
(CAMs) and adhesion receptors.

3.  Dimeric E-cadherins most commonly form
homophilic (self) cross-bridges with E-cadherins on
adjacent cells.
 Members of the Immunoglobulin (Ig) superfamily of
CAMs can form both homophilic linkages and
heterophilic (nonself) linkages.
 Heterodimeric integrins function as CAMs or as
adhesion receptors that bind to very
large, multiadhesive matrix proteins such as
fibronectin.
 Selectin dimers contain a carbohydrate-binding
lectin domain that recognizes specialized sugar
structures on glycoproteins and glycolipids on
adjacent cells.

4.  Note that CAMs often form higher-order
oligomers within the plane of the plasma
membrane.
 Many adhesive molecules contain multiple
distinct domains, some of which are found in
more than one kind of CAM.
 The cytoplasmic domains of these proteins are
often associated with adapter proteins that link
them to the cytoskeleton or to signaling
pathways.
 The evolution of CAMs, adhesion receptors, and
ECM molecules with specialized structures and
functions permits cells to assemble into diverse
classes of tissues with varying functions.

5.  CADHERINS are a family of single-pass transmembrane
glycoproteins which stick embryonic cells together in the
presence of calcium (e.g. E-cadherin in epithelial tissues; N-
cadherin in neural tissue).
 Cadherin tails are anchored to actin bundles in the
cytoskeleton by a complex called catenins ( -catenin, a
component of the Wnt signaling pathway provides a potential
link between cell signaling and cell association).

6.  Three glycoproteins
mediate Ca+2-dependent
cell adhesion:
(desmoglein
I, desmocollin I and II)
and 4 non-glycosolated
proteins located in the
attachment plaque
(desmoplakin I and
II, pakoglobin and a basic
polypeptide).
 Abundant in stratified
squamous
epithelium, which are
sites of attachment of
the cytoskeleton to the
free surface.
 Although sites of cell to Bullous pemphigold is an autoimmune disease
cell adhesion, they do not in which antibodies against desmosomal
hamper the flow of proteins are formed. This results in
substances between widespread skin & mucous membrane
cells. blistering as desmosomal proteins fall apart.

7. E-cadherin (epithethial tissue), N-cadherin (nervous tissues)
and P-cadherin (placental tissue) act to drive the adhesion of
cells of particular tissue type

8. Cadherins are required for development.
Blastomeres adhere to each other as a result
of ECM proteins the cells express on their
surfaces.

9.  CAMs (Cell Adhesion
Molecules) are single-pass
transmembrane glycoproteins
which do not require calcium
to bind to other cells.
 Neural cell adhesion
molecules (N-CAMs) are a
large family of proteins
formed by alternative
splicing.
 When embryonic tissue is
exposed to antibodies that
interact with N-CAMs, the
cells do not bind to each
other and neural tissue is not
formed.
 N-CAMs and cadherins
mediate cell-cell recognition
and cell-cell adhesion.

10.  Their carbohydrate groups
determine the strength and
specificity of cell-cell
recognition and adhesion.
 N-CAMs have repeating
chains of negatively charged
sialic acid which changes
during development.
 Expression of low sialic acid
molecules on adjacent cell
surfaces promote junction
formation on the adjacent
cell membranes.
 When the polysialic acid
residues are removed, the
two cells can adhere. The loss of sialic acid groups from
 Vesicles with N-CAMs having glycophorin may target old RBC for
little sialic acid bind tighter destruction in the spleen. The enzyme
neuraminidase can cleave the terminal
than those with large
sialic acid groups as a mechanism to
amounts. identify old RBC for retirement.

11.  INTEGRINS (I-CAMs)
are cell surface
receptors that bind the
ECM.
 They require (Ca+2 or
Mg+2), to interact with
ECM components
(fibronectin, laminin
and collagens).
 Important in epithelial
cell cohesion and
attachment to substrate
and cell migration
during tissue repair.
 Bound integrins prevent
transcription of genes
that specify apoptosis.

12. It consists of 2 large non-
covalently bound trans- The fibronectin receptor is the
membrane proteins (α and ß best characterized integrin.
subunits). A number of both
subunits combine to produce a
large variety of heterodimeric
integrins. On the outer
surface, the subunits interact
to form a binding site for the
adhesive glycoprotein, the
RGD sequence of the ECM
glycoprotein. Most of the
binding specificity depend
upon the α subunit. On the
cytosolic side, the receptor
binds components of the
cytoskeleton to enable the
ECM to communicate through
the plasma membrane to the
cytoskeleton.

13. Binding of integrins
to ECM activates
signal transduction
pathways.

14. During inflammation, leukocytes initiate attachment to the endothelial
cell surface through the SELECTINS, then stabilize the adhesion
through the interaction of an integrin and an ICAM.