CELL ADHESION

INTRODUCTION
Adhesion is binding of cells to surfaces such as ECM of another
cell
Important in maintaining multicellular structure
for instance, the lining of the small intestine, and sheets of
hepatocytes two cells thick make up much of the liver
Occur due to the action of Cell Adhesion Molecules(CAMs)
mediate homophilic (like-binds-like) adhesion between cells of a
single type and heterophilic adhesion between cells of different
types
Most CAMs are uniformly distributed along the regions of
plasma membranes

 Sometimes seen clustered Cell Junction

cytosol-facing domains of these proteins are usually connected to
elements of the cytoskeleton
So they are important in signal transduction
Involved in pathogenesis
Intractions involved are

a) hydrostatic interactions

b) electrostatic interactions

c) Brownian motion etc

Adhesion can be

a) Tight and Long lasting ( nerve cells in spinal cord)

b) Weak and Transient (immune system cells)

 CAMs
Major CAMs include

i) Cadherins

ii) Immunoglobulin superfamily

iii) Integrins

iv) Selectins

v) Mucins
2 type adhesions based on Ca2+ ions

a) Ca Dependent ( i & iv )

b) Ca Independent ( ii, iii & v )

Integrins mediate cell-matrix interactions

Others mediate cell-cell adhesion

Cadherin and the immunoglobulin (Ig) superfamily of CAMs mediate

homophilic cell-cell adhesion
Major families of cell-adhesion
molecules (CAMs)
 Cadherins
play a critical role during tissuedifferentiation
widely expressed, particularly during early differentiation are
the E-, P-, and N-cadherins.
brain expresses the largest number of different cadherins,
presumably due to the necessity of forming very specific cell-
cell contacts.
Extracellular domaincontains repeated sequences that are sites
necessary for Ca2+binding and cell-cell adhesion
cytoplasmic domain associates with thecytoskeleton
 Functions:

1) Cell sorting

2) Contact inhibition

3) Proper positioning of cell during development

4) Cellular migration

5) Supress tumor cell spread

) Types:

1) Classical ( CDH1 )

2) Desmosomal ( DSG1 )

3) Protocadherins ( PCD H1 )

4) Ungrouped ( CDH9 )
Major Cadherin Molecules on Mammalian Cells

Molecule Predominant Cellular

Distribution

E-cadherin Preimplantation
embryos, non-neural
epithelial tissue

P-cadherin Trophoblast

N-cadherin Nervous system, lens,

cardiac and skeletal
muscle
 Immunoglobulin superfamily
Calcium independent

Homophilic interaction

Active in intracellular signalling

Morphogenesis & differentiation of muscle cells/glial cells/ nerve

cells etc
In neuron it promote myelin formation

Bind with integrins/different IgSFs

Eg:-

1) Synaptic cell adhesion molecules

2) Intracellular cell adhesion molecule

3) CD2

4) CD48 etc
 Integrins
Cell- ECM adhesion

1 , 2 mediate cell-cell interaction

Important in signal transduction for cell growth regulation

Seen on cell membranes except on RBCs
Heterodimer
Multiple weak interacions lead to strong adhesion
40- 70aa long
Form focal adhesions with the help of adapter proteins like talin &
vinculin
Functions:-

1) Attachment of cell to ECM

2) Signal transduction from ECM to cell

3) Immune patroling
3) Cell migration

4) Cell growth

5) Cell division

6) Cell survival

7) Apoptosis

8) Cell differentiation

9) Forms hemidesmosomes
Eg:-

1) VLA 1

2) GP II b/ III a ( on the surface of platlets responsible for

attachment of fibrin within a developing clot)
 Selectins
cluster of differentiation 62orCD62)
single-chain transmembraneglycoproteins
calcium-dependent
bind to sugarmoietiesand so are considered to be a type
oflectin, cell adhesion proteins that bind sugarpolymers
Involved in heterophilic interactions
There are three subsets of selectins:

1) E-selectin(inendothelialcells)

2) L-selectin(inleukocytes)

3) P-selectin(inplateletsand endothelial cells)

 Structure
It have N-terminal- calcium-dependent lectin domain
anepidermal growth factor(EGF)-like domain
a variable number of consensus repeat units
a transmembrane domain (TM)
an intracellular cytoplasmic tail (cyto)
They are expressed when local inflammations occur
 Mucins
Highmolecular weight, heavilyglycosylatedproteins

key characteristic is their ability to form gels

they are a key component in most gel-like secretions

functions include

1) lubrication , cell signalling & forming chemical barriers.

2) inhibitory role

3) calcification in echinodermsand bone formation in vertebrates

4) bind to pathogens as part of the immune system.

5) Overexpression of the mucin proteins, especiallyMUC1, is associated with

many types of cancer

most mucins aresecretedontomucosal surfacesor secreted to become a

component ofsaliva
 Structure
Mature mucins are composed of two distinct regions:

The amino- and carboxy-terminal regions are very lightly

glycosylated, but rich incysteines.

The cysteine residues participate in

establishingdisulfidelinkages within and among mucin monomers.

A large central region formed of multiple tandem repeats of 10

to 80 residue sequences in which up to half of theamino

acidsareserineorthreonine.