9. Cell-cell contacts

Question 1

Fibronecins

Answer 1

Fibronecins are multiadhesive matrix proteins having heterodimer structure. Most of the time
they serve as typical extracellular matrix components of the connective tissue. Their primary
functions are to anchor the cells to the extracellular matrix components and to regulate the shape
of cells and the organisation of cytoskeleton. Fibronectins also have important roles in the
migrations and differentiation of cells during the embryonic development. Fibronectins include
cell surface fibronectins and plasma fibronectins (a soluble form in the blood). Fibronectin bind
to integrins via their RGD (arginine-glycine-aspartate) motif.

Question 2

Integrins

Answer 2

Integrins are cell surface receptors of multiadhesive matrix proteins and have heterodimer
structure (α- and β-subunits). They are important in forming cell-cell or cell-matrix interactions
and in cell signalling. The binding site on the extracellular region of the transmembrane protein
is specific for a well-defined RGD (arginine-glycine-aspartate) sequence of the ligand
molecule. They form heterophilic interactions (i.e. with other proteins) and their efficient
binding requires bivalent cations (mainly Ca2+, but sometimes Mg2+).

Question 3

cadherin

Answer 3

cadherin
Cadherins are members of a family of Ca2+
-dependent proteins that mediate the attachment of
one cell to another in animal tissues forming junctions between them. Cadherins form
homophilic interactions. For example, cells containing N-cadherin tend to cluster with other
CELL BIOLOGY – KEY WORDS version: 28 April 2023.
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cells expressing N-cadherin. Cadherin molecules are tethered to actin filaments (in adherens
junctions / adhesion belts), or cytokeratin intermediate filaments (in desmosomes) via linker
proteins inside the cell.

Question 4

RGD

Answer 4

RGD presentation
The RGD tripeptide motif is composed of arginine-glycine-aspartate amino acids and is typical
for ligands of integrins. The RGD is recognized by the binding site on the extracellular region
of integrins. These binding sites are exposed only if the integrins are activated. The necessary
change in conformation is caused by phosphorylation of the integrin intracellularly. The RGD
motif can be found in ECM macromolecules (collagen, laminin, fibronectin, vitronectin),
plasma proteins (soluble fibronectin, fibrinogen, von Willebrand factor) and cell surface
porteins (e.g. in many hormon- and neurotransmitter receptors).

Question 5

Selectins

Answer 5

selectins
Selectins have several transmembrane domains and bind the carbohydrate groups of
glycoproteins and glycolipids expressed on the surface of neighbouring cells. The lectin domain
on the end of the protein has a key role in the formation of Ca2+
-dependent binding. The
interaction created is heterophilic: a selectin binds specifically to carbon hydrate residues of
cell surface glycoproteins or glycolipids of the other cell. E-, P- and L-selectins (endothelial,
Platelet and Lymphocyte) can be distinguished.

Question 6

Extravasation

Answer 6

extravasation
The extravasation is the passage of white blood cells across intact capillary walls. Upon injuries
or infections, the expression of P-selectins increases on the surface of the endothelial cells of
capillaries by fusion of intracellular granules containing them.The P-selectins exposed interact
weakly with white blood cells slowing them down, then the white blood cells are stimulated
and their integrins are activated, undergoi conformational change and bind to ICAM-1 and
ICAM-2 molecules of the endothelial cells and form a tighter binding. White blood cells
anchored to the endothelial surface flatten and squeeze through between adjacent endothelial
cells to get into the tissue and contribute to local inflammatory reaction.

Question 7

adhesion belt

Answer 7

adhesion belt (zonula adherens)
The adhesion belt is the belt-like zone localized mainly around the epithelial cells, usually under
the tight junction, including the actin filaments attached to it from inside the cell. E-cadherin is
the transmembrane protein having a central role in the formation of the adhesion belt. In this
homophilic binding the C-terminal region of E-cadherin, which is on the cytoplasmic side,
binds to the actin skeleton through adapter proteins (e.g. catenins). It can be It gives mechanical
stability to the cell associations.

Answer 8

desmosomes (macula adherens)
Desmosomes are plaque-like junction structures between cells which link cells mechanically to
each other. The cell-cell connection is ensured by special cadherins (desmoglein and
desmocollin molecules). Inside the cell the plaque is attached to intermediate filaments.
hemidesmosome
Hemidesmosomes attach the cell to the extracellular matrix. Hemidesmosomes are
asymmetrical and are found in epithelial cells connecting the basal surface of the cell to the
basal lamina. The transmembrane integrin molecules connect the proteins of the extracellular
matrix to the intermediate filaments of the cytoskeleton.

Answer 9

focal adhesion
Focal adhesion plaques bind the microfilaments (actin fibers) of cells to extracellular matrix
molecules via integrin molecules. Vinculin-, talin- and α-actinin molecules are involved in the
attachment of the intracellular region of integrin molecules to actin filaments.
tight junction (occluding zone)
Cell–cell junction composed of a double layer of claudin and occludin molecules that seals
adjacent epithelial cells tightly together, running around each cell body close to the apical
surface. It prevents the passage of most dissolved molecules from one side of the epithelial
sheet to the other. It also confines specific membrane proteins to either the apical or the
basolateral membrane of the cell, thereby allowing directional transcellular transport.