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 tissue differentiation
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 domain contains repeated sequences that are sites

necessary for Ca2+ binding and cell-cell adhesion

cytoplasmic domain associates with the cytoskeleton

 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 62 or CD62)

single-chain transmembrane glycoproteins

calcium-dependent

bind to sugar moieties and so are considered to be a type

of lectin, cell adhesion proteins that bind sugar polymers

Involved in heterophilic interactions

There are three subsets of selectins:

1) E-selectin (in endothelial cells)

2) L-selectin (in leukocytes)

3) P-selectin (in platelets and endothelial cells)

 Structure

It have N-terminal- calcium-dependent lectin domain

an epidermal 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
High molecular weight, heavily glycosylated proteins

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 echinoderms and bone formation in vertebrates

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

5) Overexpression of the mucin proteins, especially MUC1, is associated with

many types of cancer

most mucins are secreted onto mucosal surfaces or secreted to become a

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

The amino- and carboxy-terminal regions are very lightly

glycosylated, but rich in cysteines.

The cysteine residues participate in

establishing disulfide linkages 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 the amino

acids are serine or threonine.