Cell Cell interactions
Cell cell adhesions are additionally mediated by plasma membrane call adhesion
molecules.
Collections of adhesion molecules form cell junctions that join cells together within
tissues. There is an increasing recognition that adhesion is involved in the
pathogenesis of many different diseases including viral infection cardiovascular
disease and bone joint disease.
The development of a more complete understanding of the fundamental process of
cell adhesion will likely lead us to a better understanding of such diverse pathologies.
Cell adhesion molecules
Cell adhesion molecules mediate selective cell to cell and cell to ecm adhesion.
There are all transmembrane proteins that are embedded within the plasma
membranes of cells. They extend from the cytoplasm through the plasma membrane
to the extracellular space. In the extracellular space they bind specifically to their
ions . the ions may be cell adhesion molecules on other cell or components of the
ECM. Four families of adhesion molecules function in cell cell adhesion.
1.Cadherins : the cell adhesion molecules that are important in holding cells togetter
to maintain the integrity of a tissue are called the cadherins. There transmembrane
linker proteins contain extracellular that bind to a cadherin on other cell. Calcium is
required for cadherins is important in maintaining the tissue structure.
2.Selectins : the selectins are particularly important in the immune system in white
blood cell. The selectins are named for their “lectin”. A selectin on one cell interacts
with a carbohydrate-containing ligand on another cell.
3.Immunoglobulin : is antibodies these some immunoglobulin superfamily members
facilitate adhesion of leukocytes to endothelial cells lining the blood vesssels during
injury and stress. Ligands for this family of adhesion molecules include other
members of the immunoglobulin superfamily as well as integrins.
4.Integrins : Both cell cell and cell to ecm adhesions are mediated by integrins.
Members of this family of homologous transmembrane , heterodimeric proteins bind
to their ligands with relatively low affinity ; multiple weak adgesive interactions
characterize integrin binding and function. Integrins consist of two transmembrane
chains α and β with combinations of 18 α subunits and 8 β subunits forming 24
different integrins
Cell junctions
Are a class of cellular structures consisting of multiprotein complexes that provide
contact or adhesion between neighboring cells or between a cell and
the extracellular matrix in animals. They also maintain the paracellular barrier
of epithelia and control paracellular transport. Cell junctions are especially abundant
in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix,
cell junctions help hold animal cells together
Tight junctions
Found in vertebrate epithelia, tight junctions act as barriers that regulate the
movement of water and solutes between epithelial layers. Tight junctions are
classified as a paracellular barrier which is defined as not having directional
discrimination; however, movement of the solute is largely dependent upon size and
charge. There is evidence to suggest that the structures in which solutes pass
through are somewhat like pores.
Physiological pH plays a part in the selectivity of solutes passing through tight
junctions with most tight junctions being slightly selective for cations. Tight junctions
present in different types of epithelia are selective for solutes of differing size,
charge, and polarity.
Proteins
There have been approximately 40 proteins identified to be involved in tight
junctions. These proteins can be classified into four major categories; scaffolding
proteins, signalling proteins, regulation proteins, and transmembrane proteins.
Roles
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Scaffolding proteins – organise the transmembrane proteins, couple
transmembrane proteins to other cytoplasmic proteins as well as to actin
filaments.
Signaling proteins – involved in junctions assembly, barrier regulation, and
gene transcription.
Regulation proteins – regulate membrane vesicle targeting.
Transmembrane proteins – including junctional adhesion
molecule, occludin, and claudin.
It is believed that claudin is the protein molecule responsible for the selective
permeability between epithelial layers.
A three-dimensional image is still yet to be achieved and as such specific information
about the function of tight junctions is yet to be determined.
gap junctions
Communicating junctions, or gap junctions allow for direct chemical communication
between adjacent cellular cytoplasm through diffusion without contact with the
extracellular fluid.This is possible due to six connexin proteins interacting to form a
cylinder with a pore in the centre called a connexon.The connexon complexes
stretches across the cell membrane and when two adjacent cell connexons interact,
they form a complete gap junction channel. Connexon pores vary in size, polarity
and therefore can be specific depending on the connexin proteins that constitute
each individual connexon. Whilst variation in gap junction channels do occur, their
structure remains relatively standard, and this interaction ensures efficient
communication without the escape of molecules or ions to the extracellular fluid.
Gap junctions play vital roles in the human body, including their role in the uniform
contractile of the heart muscle. They are also relevant in signal transfers in the brain,
and their absence shows a decreased cell density in the brain. Retinal and skin
cells are also dependent on gap junctions in cell differentiation and proliferation
Adhesion junction
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Cell–cell adhesion is a selective process such that cells adhere only to other
cells of specific types.
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Cells from one tissue (e.g., liver) specifically adhere to cells of the same
tissue rather than to cells of a different tissue (e.g., brain).
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Such selective cell–cell adhesion is mediated by transmembrane proteins
called cell adhesion molecules, which can be divided into four major groups:
the selectins, the integrins, the immunoglobulin (Ig) superfamily, and the
cadherins
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Cell adhesion mediated by the selectins, integrins, and most cadherins
requires Ca2+, Mg2+, or Mn2+, so many adhesive interactions between cells
are divalent cation-dependent.
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The selectins mediate transient interactions between leukocytes and
endothelial cells or blood platelets.
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There are three members of the selectin family: L-selectin, which is expressed
on leukocytes; E-selectin, which is expressed on endothelial cells; and Pselectin, which is expressed on platelets.
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The selectins recognize cell surface carbohydrates.
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One of their critical roles is to initiate the interactions between leukocytes and
endothelial cells during the migration of leukocytes from the circulation to sites
of tissue inflammation.
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The selectins mediate the initial adhesion of leukocytes to endothelial cells.
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This is followed by the formation of more stable adhesions in which integrins
on the surface of leukocytes bind to intercellular adhesion molecules (ICAMs),
which are members of the Ig superfamily expressed on the surface of
endothelial cells.
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The firmly attached leukocytes are then able to penetrate the walls of
capillaries and enter the underlying tissue by migrating between endothelial
cells.
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The binding of ICAMs to integrins is an example of a heterophilic interaction in
which an adhesion molecule on the surface of one cell (e.g., an ICAM)
recognizes a different molecule on the surface of another cell (e.g., an
integrin).
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Other members of the Ig superfamily mediate homophilic interactions in which
an adhesion molecule on the surface of one cell binds to the same molecule
on the surface of another cell.
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Such homophilic binding can lead to selective adhesion between cells of the
same type.
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For example, neural cell adhesion molecules (NCAMs) are members of the Ig
superfamily expressed on nerve cells, and homophilic binding between
NCAMs contributes to the formation of selective associations between nerve
cells during development.
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There are more than 100 members of the Ig superfamily, which mediate a
variety of cell–cell interactions.
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The fourth class of cell adhesion molecules is the cadherins.
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Cadherins are involved in selective adhesion between embryonic cells and
the formation of specific synapses in the nervous system, and they are the
proteins primarily responsible for the maintenance of stable junctions between
cells in tissues.
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Cadherins are a large family of proteins (more than 100 members) that share
a highly conserved extracellular domain that mediates largely homophilic
interactions.
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For example, E-cadherin is expressed on epithelial cells, so homophilic
interactions between E-cadherins lead to the selective adhesion of epithelial
cells to one another.
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Loss of E-cadherin can contribute to the development of cancers arising from
epithelial tissues.
Cell–cell interactions mediated by the selectins, integrins, and most members of the
Ig superfamily are generally transient, although Ig superfamily proteins (NCAM, for
example) participate in forming stable junctions between neurons at synapses
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These cell–cell junctions are of two types: adherens junctions and
desmosomes