CELL ADHESION

MOLECULES

Mrs. OFELIA SOLANO SALUDAR

Department of Natural Sciences
University of St. La Salle
Bacolod City
Major families of cell-adhesion molecules
(CAMs) and adhesion receptors.
 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.
 Selectin dimers contain a carbohydrate-binding lectin
domain that recognizes specialized sugar structures on
glycoproteins and glycolipids on adjacent cells.
 Heterodimeric integrins function as CAMs or as adhesion
receptors that bind to very large, multiadhesive matrix
proteins such as fibronectin. 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.
 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).
 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 cell
adhesion, they do not hamper
the flow of substances
between cells. Bullous pemphigold is an autoimmune disease in
which antibodies against desmosomal proteins are
formed. This results in widespread skin & mucous
membrane blistering as desmosomal proteins fall apart.
 E-cadherin (epithethial tissue), N-cadherin (nervous tissues) and P-
cadherin (placental tissue) act to drive the adhesion of cells of particular
tissue type
Cadherins are required for development. Blastomeres
adhere to each other as a result of ECM proteins the
cells express on their surfaces.
 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.
 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 glycophorin
 Vesicles with N-CAMs having may target old RBC for destruction in the
little sialic acid bind tighter than spleen. The enzyme neuraminidase can cleave
the terminal sialic acid groups as a mechanism
those with large amounts.
to identify old RBC for retirement.
 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.
 It consists of 2 large non-covalently
bound trans-membrane proteins (α The fibronectin receptor is the best
and ß subunits). A number of both characterized integrin.
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.
Binding of integrins to
ECM activates signal
transduction pathways.
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.
?