GOOD

MORNING

CELL JUNCTIONS
Dr. LUBNA FIRDOSE
FAROOQIA DENTAL COLLEGE
MYSORE.

Overview.
Introduction.
Definition.
Classification.
Types.
Clinical

Correlation.

Introduction
The plasma membrane is the surface which
establishes contact with other cells and with
structural components of extracellular
matrices.
These contacts may have a predominantly
adhesive role, or initiate instructive signals
within and between cells, or both.
They frequently affect the behaviour of cells.

Definition
A specialized site on a cell at which it
is attached to another cell or to the
extracellular
matrix.(cell
and
molecular biology).
Cell junctions are the specialized
connections between the plasma
membranes of adjoining cells.

 Cell

junctions consist of multiprotein

complex that provide contact between
neighbouring cells or between a cell and
the extra cellular matrix.
They also build up the paracellular
barrier of epithelia and control the
paracellular transport.
Cell junctions are especially abundant
in epithelial tissues.

Two main ways in which animal cells are bound tog

Structural classification of cell

junctions.
Specialised adhesive contact

Generalised adhesive contact.

Occluding
junctions.
Calcium
Adhesive
dependent.
junctions.
.Cadherins.
Gap junctions
.Selectins.
.Integrins.

Calcium
independent.

.Neural cell
adhesion
molecules.
.Intercellular
adhesion
molecules.

Four functional classes of cell junctions in animal tissues

Anchoring junctions.
Anchoring junctions are widely distributed
and most abundant in tissues that are
subjected to severe mechanical stress, such
as heart, muscle, and epidermis.
They are composed of two main classes of
protein.
Intracellular anchor proteins .
Transmembrane adhesion proteins

Transmembrane adhesion proteins link the cytoskeleton to

extracellular structures

Adherens junction
Cell junction in which the cytoplasmic
face of the plasma membrane is attached
to actin filaments.
Example : adhesion belts.

In
epithelia,they
form
continuous adhesion belt (or zonula
adherens) just below the tight junctions.
The adhesion belts are directly apposed in
adjacent epithelial cells, with the
interacting plasma membranes held
together by the cadherins that serve here
as transmembrane adhesion proteins.

The actin is attached to this membrane

through a set of intracellular anchor
proteins, including catenins, vinculin, and actinin.
This network can contract with the help of
myosin motor proteins.
It is thought to help in mediating a
fundamental
process
in
animal
morphogenesis-the folding of epithelial cell
sheets into tubes and other related
structures.

CADHERIN

Classical Cadherins.
E - Cadherin.
N - Cadherin.
P - Cadherin.

Non Classical
cadherins.
Desmocollin.
Desmoglein.
T - Cadherin

Cadherins mediate homophilic adhesion

Desmosome
Type of anchoring cellcell junction,
characterized by dense plaques of protein into
which intermediate filaments in the two
adjoining cells insert.
Desmosomes
are buttonlike points of
intercellular contact that rivet cells together.
They serve as anchoring sites for ropelike
intermediate filaments, which form a

structural framework of great tensile

strength .

Through desmosomes, the intermediate

filaments of adjacent cells are linked into
a net that extends throughout the many
cells of a tissue.
The particular type of intermediate
filaments attached to the desmosomes
depends on the cell type: they
are keratin filaments in most epithelial
cells, and desmin filaments in heart
muscle cells.

Intracellular
anchor
proteins
(plakoglobin and desmoplakin) that are
responsible
for
connecting
the cytoskeleton to the transmembrane
adhesion proteins.

These
adhesion
proteins
(desmoglein and desmocollin), belong to
the cadherin family.
They interact through their extracellular domains
to hold the adjacent plasma membranes together.
The importance of desmosome junctions is
demonstrated by some forms of the potentially
fatal skin disease pemphigus.

Focal adhesions
Focal adhesions (cellmatrix adhesions) are
specific
types
of
large
macromolecular
assemblies through which both mechanical force
and regulatory signals are transmitted.
Focal adhesions serve as the mechanical linkages to
the ECM, and as a biochemical signaling hub to
concentrate and direct numerous signaling proteins
at sites of integrin binding and clustering.

Structure and function

Focal

adhesions
are
large,
dynamic protein complexes through
which the cytoskeleton of a cell
connects to the extracellular matrix.
Focal adhesions can contain over 100
different proteins, which suggests a
considerable functional diversity.

More than anchoring the cell, they

function as signal carriers (sensors),
which inform the cell about the condition
of the ECM.
Their important role is in the immune
system, in which white bloodcells migrate
along
the
connective endothelium following cellular
signals to damaged biological tissue.

Morphology
Connection between focal adhesions and
proteins
of
the
extracellular
matrix generally involves integrins.
Integrins bind to extra-cellular proteins
via short amino acid sequences, such as
the R-G-D sequence motif (found in
proteins such as fibronectin, laminin,
or vitronectin), or the DGEA and
GFOGER motifs found in collagen.

 Integrins

are heterodimers which

are formed from one beta and one
alpha subunit.
These subunits are present in
different forms, which differ in
their specificity and affinity to the
different ECM proteins.

Hemidesmosome
Specialized

anchoring
cell
junction between an epithelial cell
and the underlying basal lamina.
Hemidesmosomes,
resemble
desmosomes morphologically and in
connecting to intermediate filaments,
and they act as rivet to distribute
tensile or shearing forces through an
epithelium.

The extracellular domains of the integrins bind to

a laminin protein in the basal lamina, while an
intracellular domain binds via an anchor
protein (plectin) to keratin intermediate filaments.
Whereas the keratin filaments associated with
desmosomes make lateral attachments to the
desmosomal plaques many keratin filaments
associated with hemidesmosomes have their ends
buried in the plaque

Integrins in the plasma membrane anchor a cell

to extracellular matrix molecules.
cadherin family members in the plasma
membrane anchor it to the plasma membrane of
an adjacent cell.
In both cases, there is an intracellular coupling
to cytoskeletal filaments, either actin filaments
or intermediate filaments.

Thin, extracellular, electron-dense lines, parallel to

the plasma membrane, subjacent to the outer plaque
are visible in one third of HDs and are termed subbasal dense plates (SBDPs).
Anchoring
filaments
traverse
the
lamina
lucida space and appear to insert into the electron
dense zone, the lamina densa.
Beneath the lamina densa, loop-structured, crossbanded anchoring fibrils extend more than 300 nm
beneath the basement membrane within the papillary
dermis.

Occluding junctions
Tight junctions, also known as zonula
occludens, are the closely associated
areas of two cells whose membranes join
together forming a virtually impermeable
barrier to fluid.
It is a type of junctional complex present
only in vertebrates.

The role of tight junctions in transcellular

transport

Transport

proteins are confined to

different regions of the plasma
membrane in epithelial cells of the
small intestine.
These junctions also block the
backflow
of
glucose
from
the basal side of the epithelium into
the gut lumen.

 Extracellular

tracer molecule added on

one side of an epithelium cannot traverse
the tight junctions that seal adjacent cells
together.
Extracellular,
electron-dense
tracer
molecule added to either the apical side
or the basolateral side In both cases, the
tracer is stopped by the tight junction.

 The

major transmembrane proteins in a

tight junction are the claudins, which
are essential for tight junction
formation and function and differ in
different tight junctions.
A
second major transmembrane
protein
in
tight
junctions
is occludin, the function of which is
uncertain.

Claudins and occludins associate

with
intracellular
peripheral
membrane
proteins
called ZO proteins which anchor the
strands to the actin cytoskeleton.

A current model of a tight junction

Septate junction

septate junctions are the occluding junction.

More regular in structure than a tight junction.
They form a continuous band around each epithelial
cell..
But their morphology is distinct because the interacting
plasma membranes are joined by proteins that are
arranged in parallel rows with a regular periodicity.
A protein called Discs-large, which is required for the
formation of septate junctions is Drosophila.

Gap junction
Gap junction or nexus is a specialized
intercellular connection between a multitude of
animal cell-types.
It directly connects the cytoplasm of two cells,
which allows various molecules and ions to pass
freely between cells,
One gap junction channel is composed of
two connexons (or hemichannels) which
connect across the intercellular space .

Each
gap
junction
appears
in
conventional electron micrographs as a patch
where the membranes of two adjacent cells are
separated by a uniform narrow gap of about 2
4 nm.
The gap is spanned by channel-forming
proteins (connexins). The channels they
form (connexons) allow inorganic ions and other
small water-soluble molecules to pass directly
from the cytoplasm of one cell to the cytoplasm
of the other,

Functions of gap junction protein.

Electrical and metabolic coupling between
cells
Electrical and metabolic exchange through
hemichannels
Adhesive
function
independent
of
conductive gap junction channel (neural
migration in neocortex)
Role of carboxyl-terminal in signaling
cytoplasmic pathway.

Gap Junctions Have Diverse Functions

In tissue containing electrically excitable
cells- electrical coupling through gap
junctions synchronizes the contractions of
both heart muscle cells and the smooth
muscle cells responsible for the peristaltic
movements of the intestine.
Cell coupling via gap junctions also seems
to be important in embryogenesis.

Plasmodesmata
Extend

through pores in the cell wall

connecting the cytoplasm of each cell
with that of its neighbors.

Chemical synapses
Chemical synapses are specialized junctions
through which neurons signal to each other and to
non-neuronal
cells
such
as
those
in muscles or glands.
Chemical synapses allow neurons to form circuits
within the central nervous system.
They allow the nervous system to connect to and
control other systems of the body.

Synaptic
vesicle.

Neurotransmitter.
Reuptake pump.

Post synaptic
density.

Receptor.

At a chemical synapse, one

neuron
releases neurotransmitter molecules into
a small space that is adjacent to another
neuron.
The neurotransmitters are kept within
small sacs called vesicles, and are released
into the synaptic cleft by exocytosis.
These molecules then bind to receptors on
the postsynaptic cell's side of the synaptic
cleft.

Epithelium Connective tissue

interface.
Epithelium is separated from the unnderlying
connective tissue by a thin sheet known as Basal
lamina.
Basal lamina has a thickness of 50 to 100nm.
It consists of two structural components Lamina
lucida and Lamina densa.
Between lamina lucida and connective tissue
there is third layer the Lamina fibroreticularis.

Constituents of basal lamina.

Type IV collagen .
Adhesive
glycoproteinlaminin,fibronectin.
Heparin sulfate proteoglycan.
Type III collagen-reticular fibers.
Type VII collagen-anchoring fibrils.

Functions.
Attaches

epithelium to underlying
connective tissue.
Acts as a filter to control the
movements of molecules.
Acts as a barrier to cell migration.
Has important signalling function.

Disorders of epithelial attachment.

Genetic
1. Dystrophic
epidermolysis
bullosa.
2. Junctional
epidermolysis
bullosa,
3. Epidermolysis
bullosa simplex.
4. Epidermolytic
hyperkeratosis.

Autoimmune
1. Cicatricial
pemphigoid.
2. Bullous
pemphigoid.
3. Pemphigus
vulgaris.
4. Pemphigus
foliaceus.

REFERENCES
Ham AW, Cormack DH. Hams Histology. 9th
ed. Lippincott Williams and Wilkins;
1987.p.143-9.
Nanci A. Tencates Oral Histology.7th ed.Mosby
Elsevier; 2008.p. 57-65.
Singh I. Human Histology. 3rd ed.Jaypee
Medical publisher;1997. p. 9-14.
Stranding S. Grays Anatomy:The Anatomical
Basis of clinical practice.39th ed. Edinburg:
Elsevier Churchill Livington; 2008.p. 6-10.

Alberts B, Johnson A, Lewis J, Raff M,

Roberts K, Walter P. Molecular Biology of
cell. 4th ed. Garland Science; 2002. P.41-6.
Garant P R. Oral Cells and Tissues. 1st ed.
Quintessence publishing.co,inc;
2003.p.101-13.

THANK YOU.