Cell adhesion notes

1. Cell-cell Adhesion
Dr. Tripti Singh
School of Biosciences

2. Cell-cell adhesion
• Cell adhesion is the ability of a single cell to stick to another
cell or an extracellular matrix (ECM).
• Cell adhesion molecules are proteins that help cell stick to
each other and to the surroundings.
• Adhesion plays an integral role in cell communication and
regulation, and is of fundamental importance in the
development and maintenance of tissues.

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• Cell adhesion is involved in stimulating signals that regulate
cell differentiation, cell cycle, cell migration, and cell survival.
• According to the “cell adhesion model”, the more a cell sticks
the more it shows the greater number of chemical bonds it has
on its surface.

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• Changes in cell adhesion can be the defining event in a wide
range of diseases including arthritis, atherosclerosis,
osteoporosis, and cancer .
• Cell adhesiveness is generally reduced in human cancers.
Reduced intercellular adhesiveness allows cancer cells to
disobey the social order, resulting in destruction of histological
structure, which may be related to the invasive and metastatic
potential.

5. Importance cell adhesion
• It is important for:
• Tissue formation during morphogenesis
• cell migration
• Regulation of : cell proliferation, gene expression and cell
death (apoptosis)

6. Integral membrane protein parts:
• Integral membrane protein embedded in the phospholipid
bilayer , and has free major portions.
• The portion of the protein that spends the membrane, called
trans- membrane region (TMR).
• The extracellular domain of the protein (ECD).
• The intracellular domain of the protein (ICD).

7. Integral membrane protein

8. • Types of cell adhesion molecules (CAMs) binding:
• Homophilic binding: If the cell adhesion molecules between
two neighboring cells are the identical. (Cadherin-Cadherin)
• Hetrophilic binding: If the cell adhesion molecules between
two neighboring cell are not identical. (Selectin-Mucin)

10. • Cell adhesion molecules
• 1.Immunoglobulin super family cell adhesion
molecules
• 2.Integrin
• 3.Selectin
• 4.Cadherin

11. CELL ADHESION MOLECULES
• Immunoglobulin super family cell adhesion molecules (IgSF
CAMs):
• Structure:
• The trans-membrane region of all the IgSF-CAMs is a single
alpha helix span the membrane. (one protein)
• Inside and outside we have extracellular domain

12. Example:
• 1.Intercellular adhesion molecule-1 (ICAM-1): It is expressed
in the apical membrane of endothelial cells (mainly capillary
and post capillary venues).
• When there is an invading pathogen, the endothelial cells
become activated and will express ICAM-1 on their surfaces.
• ICAM-1 will bind to cell adhesion molecule LFA-1
(Lymphocyte function associated -1, Integrin molecule)
expressed on monocytes.
• Monocytes will move across the endothelial cells to the
interstitial space to differentiate to macrophage.

13. Vascular cell adhesion molecule-1 (VCAM-1):
• Its is expressed in the apical membrane of endothelial cells.
• When there is an invading pathogen, the endothelial cells
become activated and will express VCAM-1 on their surfaces.
• VCAM-1 will bind to cell adhesion molecule VLA-4 (very late
antigen-4, Integrin molecule) expressed on monocytes.
• Monocytes will move across the endothelial cells to the
interstitial space to differentiate to macrophage.

14. • Platelet endothelial cell adhesion-1 (PCAM-1)= CD31:
• Endothelial cells posses three types of junctions:
• I.Tight junction
• II.Adherent junction
• III.Two PCAM-1 protein on the opposing endothelial cell
membranes. ( Homophilic binding )

15. Integrin
2.Integrin:
• Structure: The protein is formed of two subunits, α and β
subunit. there are 18 α and 8 β subunit type, however, only 24
types found in human body )
• Has a large extracellular domain.
• Single membrane spanning α helix.
• A very small intracellular domain.

16. • Example:
• 1.Lymphocyte function-associated antigen–1(LFA-1):
• LFA-1= α11 β2 = αL β2
• Found on the surface of all leucocytes and mainly on the
monocyte.
• In the inflammatory state, the endothelial cells starts to express
the ICAM-1 on its surface to bind to LFA-1 of the monocytes
> differentiate to macrophage in the interstitial space.
• 2.Very late antigen-4 (VLA-4):
• VLA-4 = α4 β1
• Found on the surface of the monocyte.
• In the inflammatory state, VLA-4 binds to VCAM-1.

17. • 3.Integrin bind directly to collagen:
• α1 β1
• α2 β1
• 4.Integrin bind indirectly to collagen:
• First bind to Fibronectin
• α5 β1

18. Cadherin
• 3.Cadherin superfamily:
• Extra cellular cadherin domain range from (1-34) domains.
• All cadherin are a trans membrane protein except T-cadherin.
• Types of Cadherin:
• 1.Type I classical cadherin
• 2.Type II a typical cadherin
• 3.Truncated cadherin
• 4.Desmosomal cadherin
• 5.Flamingo cadherin
• 6.Proto cadherin
• 7.Others

19. Types of Cadherin:
• 1. T- cadherin is completely outside the cell membrane and
attached to it by a lipid called Glycosyl phosphatidylinositol
(GPI).
• 2.Type I classical cadherin: It produce cell to cell direct
connection. (Adherent Junction)
• Example:
• E- Cadherin: found in the epithelial cells
• N - Cadherin: found in the neuron, muscle tissue
• P - Cadherin : found in the placenta, epidermis

20. • Structure:
• They all have 5 extracellular cadherin domain ended with
amino terminal NH2.
• The N terminal of the Extra cadherin domain will bind to
the neighboring N terminal of the EC domain.
• The binding is dependent to the extra cellular Ca ions.

21. 3.Desmosomal Cadherin:
• Types: Desmocollin (1,2,3) and Desmoglein (1,2,3,4)
• Structure:
• They all have 5 extracellular cadherin domain ended with NH2. (1 E
anchor domain and 4 EC domains distally).
• The N terminal of the Extra cadherin domain will bind to the neighboring
N terminal of the EC domain.
• The cytoplasmic terminal end binds to 2 proteins:
• 1.Plakoglobin= γ catenin
• 2.Plakophilin
• These two proteins will bind to desmoplakin intermediate filament
(Keratin)
• The binding is dependent to the extra cellular Ca ions.

22. The extracellular core allows water and ions flow in between the cells.
E.g: Skin, Intestins

23. Selectin
• Selectins:
• Example:
• 1.P- Selectin: Found on the endothelial cells to help the recruitment
of the neutrophils, P-Selectin glycoprotein ligand 1, type 1
activation (induced by histamine and induced in minutes) .
• 2.E-Selectin: Found on the endothelial cells and binds to Sialyl-
Lewis X found always on the surface of the neutrophil type 2
activation (takes hours).

24. • L-Selectin:
• The high endothelial cells allows the naïve T lymphocytes to
move from the blood into lymph nodes and back out.
• Naïve T-lymphocytes have on their surface the L-Selectin
that binds to GLYCAM-1 on the high endothelial cells
movement of the lymphocyte to the Lymph node.