CELL – CELL JUNCTIONS

Adhesion Junctions

• Cell-cell adhesion is a selective process mediated by cell adhesion molecules

(CAMs).
• They are divided into four major groups namely selectins, integrins, immunoglobulin
(Ig) super family, and cadherins.
• Cell adhesion mediated by selectins, integrins, and most cadherins requires Ca2+,
Mg2+ or Mn2+ .
• The selectins are membrane glycoproteins with a calcium dependent lectin domain
that is important for carbohydrate recognition and cell adhesion.
• There are three types of selectins namely, L-selectin, which is constitutively expressed
on variety of leukocytes; E-selectin is expressed on activated endothelial cells; and P-
selectin, that is expressed on platelets and activated endothelial cells.
• The selectin family mediates transient interactions (rolling adhesion) between
leukocytes and endothelial cells.
• The weak adhesive interactions help to slow down circulating leukocytes allowing
time to sense the signals before exiting circulation.
• The ligands for selectins are members of the sialomucin family.
• The weak cell-cell interactions are followed by stronger interactions involving β2-
integrins subfamily members expressed on surface of leukocytes and Ig super family
CAMs such as intercellular adhesion molecules (ICAMs) on endothelial cells.
• The firm binding of leukocytes is an essential step for transendothelial migration.
• Cadherins are a large family of calcium dependent transmembrane glycoproteins
involved in selective adhesion between embryonic cells, formation of specific
synapses in the nervous system and maintenance of stable junctions between cells
in tissues.
• They share a highly conserved extracellular domain and mediate largely homophilic
interactions.

Anchoring Junctions

• Anchoring junctions connect the cytoskeleton of one cell to that of its neighbouring
cell (cell-cell junction) or to the ECM (Cell-matrix junction).
• They are most abundant in animal tissues that are subject to mechanical stresses.
• The basic components of these junctions are cell adhesion proteins and anchor
proteins.
• Adherens junctions are commonly found in epithelia such as lining of the intestine,
where they occur as “adhesion belts” (or zonula adherens) to encircle cells near its
apical surface.
• In an adherens junction, cells are held together by calcium-dependent linkages
formed between extracellular domains of cadherin molecules.
• The basic structural unit of an adherens junction includes anchor proteins β-catenin
and α-catenin in addition to transmembrane cadherins. β-catenin binds directly to the
 cytosolic tail of the cadherins whereas, α-catenin binds to β-catenin as well as to actin
filaments and actin filament-binding proteins, such as vinculin.
• Associated with the cadherins is the β- catenin related protein p120.
• The cadherin clusters of an adherens junction connect the external environment to
actin bundles of epithelial cells by forming a transcellular network and create a
pathway for signal transduction.

Desmosomes

Desmosomes (or maculae adherens) are disk-shaped adhesive junctions found

particularly in tissues subjected to mechanical stress such as cardiac muscle,
epithelial layers of skin and uterine cervix. Desmosomes directly link the intermediate
filament of adjacent cells across a narrow extracellular gap and assemble an
integrated unit of great tensile strength. The cadherins of desmosomes have a
diTerent domain structure and are called desmogleins and desmocollins. Their
cytosolic tails is bound to plakoglobin and plakophilin that provide a direct link to the
intermediate filament binding protein, desmoplakin.

Hemidesmosomes

• The basal surface of epithelial cells is anchored to the underlying basement membrane
by a specialized adhesive structure called hemidesmosomes or half desmosomes.
• It resembles desmosomes and they also connect to intermediate filaments (keratin) of
adjacent cells, but the transmembrane glycoproteins in hemidesmosomes are integrins
rather than cadherins.
• Hemidesmosomes contain a dense plaque on the inner surface of plasma membrane
with keratin filaments (intermediate filament) pointing into the cytoplasm that are
linked to the ECM by integrins via an anchor protein, plectin.
• The extracellular domains of the integrins bind to laminin to mediate adhesion.
• The hemidesmosomes facilitate association of intermediate filaments of adjacent cells
into an extended network which help to distribute shearing forces across the
epithelium.

Focal adhesions

• Focal adhesions are dynamic structures that can be rapidly disassembled if the
adherent cell is stimulated to move or enter mitosis.
• The plasma membrane in the region of a focal adhesion contains large clusters of
integrins.
• The integrins can reversibly switch between active and inactive states and this dictates
their ability to bind matrix components.
• The cytoplasmic domains of integrins are connected via adaptors to actin filaments.
• Focal adhesions may act as a type of sensory structure, collecting information about
extracellular environment and transmitting it to the cell interior, which may lead to
changes in cell adhesion, proliferation, or survival.
• Focal adhesions also help in cell locomotion.
• They are capable of creating or responding to mechanical forces, which might be
expected from a structure that contains actin and myosin.

Tight junctions or Zonula Occludens

• Tight junctions (TJs) are the closest known contacts located at apical end of junctional
complex between neighbouring epithelial cells in vertebrates.
• They are also present between endothelial cells that line the walls of capillaries.
• This is particularly evident in brain where they form the blood–brain barrier, which
prevents substances from passing from bloodstream into the brain.
• Essentially tight junctions perform two important functions.
• They form seals that prevent free passage of molecules (including ions) between cells
of epithelial sheets.
• TJs also serve as “fences” to maintain polarized character of epithelial cells by not
permitting diTusion of some membrane proteins and lipids between apical and
basolateral parts of the membrane.
• In all cases the seal is not foolproof; they are permeable to the small molecules to
varying degrees.
• The integral proteins of TJs form continuous fibrils that completely encircle the cell and
make contacts with neighbouring cells on all sides.
• Each strand in these networks is composed of TM proteins of claudin, occludin, and
junctional adhesion molecule (JAM) families.
• These proteins bind to similar proteins on adjacent cells, thereby sealing the space
between their plasma membranes.
• The cytosolic tails of claudins, occludins, and JAMs are also associated with proteins of
the zonula occludens family, which link the tight junction complex to the actin
cytoskeleton and hold it in place on the plasma membrane.

Communicating Junctions

Communicating junctions as the name suggests will permit the movement of low
molecular weight metabolites, ions, vitamins and even signaling molecules between
adjacent cells.

Gap Junctions

• In animal cells gap junctions are sites where plasma membranes of adjacent cells
come very close to one another but do not make direct contact.
• Instead, the cleft between cells is spanned by very fine strands (molecular “pipelines”)
that passes through adjoining plasma membranes and opens into the cytoplasm of
neighbouring cells.
• Consequently, gap junctions couple both metabolic activities and electric responses of
the cells they connect such as epithelial cells, endothelial cells, and cells of cardiac
and smooth muscles.
• Gap junctions are composed of a transmembrane protein, connexins. The connexins
proteins are organized into multisubunit complexes, called connexon that completely
span the membrane.
• Each connexon is composed of six connexins subunits arranged in a ring around a
central opening, or annulus.
• The connexon on one cell then aligns with connexon of adjacent cell, forming
communicating channel between them
• Each cell forms a half channel that connects the cytoplasm of two adjoining cells.
• Most cell types express more than one type of connexins and they can assemble to form
heteromeric connexons.
• These connexons show marked diTerences in conductance, permeability and
regulation.
• Mammalian gap junctions allow diTusion of molecules below 1000 Daltons in mass.
• A number of regulatory substances, such as cyclic AMP and inositol phosphates are
small enough to pass through gap junction channels.
• As a result, gap junctions have the potential to integrate activities of individual cells of
a tissue into a functional unit.
• Gap junctions also allow cells to cooperate metabolically by sharing key metabolites,
such as ATP, sugar phosphates, amino acids, and many coenzymes.
• This is particularly important in tissues such as the lens and cornea of the eye, which
lack blood vessels.