CELL BIOLOGY

LESSON 19:
CELL ADHESION MOLECULES

Learning Objectives Local chemical mediators at the site of inflammation signal the
In this lecture, you will learn endothelial cells to express P-selectin.
• Discussion on cell adhesion molecules Nearby neutrophils express the oligosaccaride on both the
glycolipids and glycoproteins in their membrane. Thus, they are
• Their role in maintaining in integrity of cell attachments
bound at this inflammatory site by the endothelial cells
The molecules which help in cell to cell binding are called cell
Thus, they are bound at this inflammatory site by the
adhesion molecules
endothelial cells.
A. Calcium Dependent Adhesion Molecules (Cadherins) Binding is relatively weak and the cells roll along the endothelial
There are over a dozen different types of these molecules. cell until they bind more tightly by their integrins (see below).
Almost all vertebrate cells express one or more cadherins. Integrin binding is tighter and stimulates the cell to crawl out
Extracellular domains are seen. of the blood vessel

They contain about 100 amino acid residues. C. Cell to Cell binding through Special Integrins
Integrins are also transmembrane binding glycoproteins that
They contain calcium binding sites.
usually bind cells to matrix.
They bind in a homophilic pattern, i.e. one cadherin binds to
However, they also may bind cells to cells.
another in the extracellular space.
Binding is calcium dependent.
Thes molecules connects cells together at specialized junctions.
Binding is from an integrin to a specific ligand on the target cell.
They may mediate interactions between the cells’ actin
cytoskeletons. Binding may involve actin filaments, but is not associated with
a cell junction. Integrins contain an alpha and a beta subunit:
The amino acid sequence His-Ala-Val may be involved in the
Most cell to cell interactions involve integrins with an alpha and
actual “homophilic” binding.
a beta-2 subunit example. Integrins on white blood cells allow
Intracellular domain binds to specific proteins in the cytoskeletal tighter binding to endothelial cells before they migrate out of
system. the blood stream to tissue. LFA-1 (white blood cells); Mac-1
Table 3-1 Well known types of Calcium dependent (macrophages) Humans with a genetic disease called “leucocyte
adhesion molecules adhesion deficiency” are unable to synthesize the Beta-2
subunit. Thus, the white blood cells lack the entire family of
Type of What Structure: Intracellular Cytoplasmic beta-2 receptors needed to bind to endothelial cells. They
Cadherin tissues? binding filaments
proteins
suffer repeated bacterial infections.
E-Cadherin;epithelial adhesion catenins, actin D. Non-Calcium Dependent Cell to Cell binding
P-Cadherin cells belts alpha actinin They belong to the immunoglobulin (Ig) superfamily;
Desmosomal epidermis desmosomes desmoplakins keratin; NCAM’s, ICAMs and L1 are examples. They are single pass,
Cadherin and I, II; desmin
transmembrane proteins which may bind to the cytoskeletal
placenta Plakoglobin
system inside the cells. Outside the cell, the binding may be
N-Cadherin nerve, adhesion catenins, actin
muscle, belts alpha actinin, homophilic (to each other) or heterophilic (to another molecule
lens cells vinculin Cells may have N-CAMs and Cadherins, but the N-CAM
binding is not as strong as the cadherin binding.
B. Cell to Cell Surface Carbohydrate Binding Proteins Examples
(Selectins)
N-CAM (neural cell adhesion molecule) is actually expressed by
They are transient transmembrane binding proteins (lectins a variety of cell types., including nerve cells; binds by
In the presence of Calcium, they bind to specific homophilic interactions ICAM (intercellular adhesion
oligosaccharides on another cell molecules) may be expressed on activated endothelial cells.
They help in Heterophilic” cell adhesion (binding protein binds Theseare the target ligand for the integrins expressed by white
to another type of site on a cell blood cells (heterophilic binding L1 is a neural cell to cell
adhesion molecule important in developing nerve processes
Example
P-Selectins allow the initial binding of white blood cells to E. Cell to Matrix Binding: Integrins
endothelial cells Cells can be influenced heavily by the environment (matrix
proteins) because of the presence of transmembrane
glycoproteins called Integrins

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Extracellular matrix receptors that have selective affinity for

CELL BIOLOGY
certain matrix proteins. Bind with relatively low affinity (Ka=
106-109 liters/mole): this provides a “velcro effect” that allows
cells to explore their environment Binding is calcium and
magnesium dependent. Extracellular site is with a ligand in the
matrix. Intracellular site may be with proteins associated with
the actin cytoskeleton (talin and alpha actinin); some integrins
bind to intermediate filaments, however. Integrins have an
alpha and a beta subunit (heterodimer).
Subunits can be diverse (different types) by alternative splicing
Specificity of binding depends on the combination of alpha
and beta subunits
For example
Cells with alpha-6, beta-4 integrins have hemidesmosomes.
Bind matrix proteins in the basal lamina (like laminins) and
intermediate filaments, like keratins, in the cytoplasm
White blood cells have alpha1 and beta 2 integrins that bind to
endothelial cells.
Macrophages have alpham and beta 2 integrins that also bind to
endothelial cells. Platelets have beta 3 subunit in their integrins
that allows them to bind fibrinogen during blood clotting.
Humans with Glanzmann’s disease are genetically deficient in
beta 3 containing integrins. These patients bleed excessively
Cells with alpha 5 and beta 1 integrins bind fibronectin in the
extracellular matrix.

Notes

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