Intercellular junctions are specialized structures that mediate cell-to-cell and cell-to-extracellular matrix interactions. They maintain tissue integrity and control paracellular transport. The main types of intercellular junctions are tight junctions, adherens junctions, desmosomes, gap junctions, and hemidesmosomes. Tight junctions form a seal between cells to control diffusion between extracellular and intracellular spaces, while adherens junctions and desmosomes provide strong mechanical adhesion between cells. Gap junctions allow communication between cells via channels that connect their cytoplasm. Hemidesmosomes anchor cells to the extracellular matrix.

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2. INTERCELLULAR
JUNCTIONS
Presented By:
Dr. Mamta Singh
PGT - I
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3. INDEX
• Introduction
• Definitions
• Classification
• Tight junctions
• Adherens junctions
• Desmosomes
• Gap junctions
• Hemidesmosomes and focal contacts
• Cellular adhesion
• Summary
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4. INTERCELLULAR JUNCTIONS
• Specialized junctions at specific sites on the
contacting cell membrane.
• Also called as membrane junctions.
• Mediate 2 types of interactions:
1. Cell to cell
2. Cell to extracellular matrix
• Abundant in epithelial tissues.
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5. • Maintain the mechanical integrity of animal
tissues.
• Build up the paracellular barrier of epithelia.
• Control the paracellular transport.
• Provide contact between neighbouring cells or
between a cell and the extracellular matrix.
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6. • On the molecular level intercellular junctions
consists of three components:
1. Transmembrane adhesive protein
2. Cytoplasmic adapter protein
3. Cytoskeletal filament
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7. CLASSIFICATION
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INTERCELLULAR
JUNCTIONS
OCCLUDING
JUNCTIONS
COMMUNICATING
JUNCTIONS
ANCHORING
JUNCTIONS

8. • The specialized junctions may be further classified as follows:
• OCCLUDING JUNCTIONS
Tight junctions (Zona Occludens)
• COMMUNICATING JUNCTIONS
Gap junctions
• ANCHORING JUNCTIONS
Adhesive junctions
 Cell-to-cell
1. Zonula adherens (adheren junctions)
2. Macula adherens (desmosome)
 Cell-to-matrix
1. Focal adhesions
2. Hemidesmosomes 8

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10. Definitions
• Adherens junctions: A junction that links cell membranes
and cytoskeletal elements within and between cells,
connecting adjacent cells mechanically.
• Tight junctions: A junction at which adjacent plasma
membranes are joined tightly together.
• Gap junctions: Narrowed portion of intercellular space
containing channels.
• Desmosomes: Cell structure specialized for cell to cell
adhesion
• Hemidesmosomes : Link the cell to the basal lamina
and, through additional extracellular molecules, to ECM.
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11. TIGHT JUNCTIONS
• Tight junctions, or zonula occludens:
• Closely associated areas of two cells.
• Form a tight belt like adhesive seal.
• Selectively limits the diffusion of water, ions &
larger solutes as well as migration of cells.
• Separating the interior of body from the external
world.
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In electron
microscopic
structure
of thin sections of
tight junctions
the plasma
membrane of
adjacent cells
appear to fuse
together in a
series of one or
more contacts.

14. • Two structural proteins have been identified in
the structure of tight junctions namely:
• Occludins
• Claudin
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15. • A family of more than 20 proteins, called
Claudins, constitutes the main structural
proteins of tight junction strands.
• Claudins have four transmembrane sequences,
but they are not related in sequence to occludin.
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A.Preliminary model
of tight junction
structure with claudin
linking the two
membranes together
& peripheral protein
ZO-1 linking the
cytoplasmic tail of
claudin to actin
filaments.
B-C. transmembrane
topology of claudin &
occludin.

17. Tight junctions
• Extracellular domains of claudins form rows of pores along tight
junction.
• Each claudin has a unique selectivity for cations or anions.
• At the zona occludens the membranes of adjoining cells
converge and are at a distance of 0.1- 0.3 µm.
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18. • Human gingival keratinocytes (HGKs) were studied by
means of freeze-fracture technique for the investigation
of intercellular contacts.
• In vivo the tight junctions, which were of low complexity
were co-distributed with desmosomes; in one case, the
strands ran directly through desmosomal plaques.
• Where tight junctions and desmosomes occurred
together, no gap junctions were seen.
• In contrast, where no tight junctions were present, gap
junctions and desmosomes were co-localized.
Meyle J, Güttig K, Rascher G and Wolburg H: Transepithelial electrical resistance and tight
junctions of human gingival keratinocvtes. J Periodont Res 1999; 34: 214–222
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19. • Adherens junctions and Desmosomes are
two types of adhesive junctions using homophilic
interactions of cadherins to bind epithelial cells
to adjacent cells.
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20. ADHERENS JUNCTIONS
• The zonula adherens is a band like specialization of the
membrane and cytoplasm that encircles the apex of
adjoining cells and strongly bonds the cells together.
• In this junction the opposing membranes are 15 – 20 nm
apart .
• It is a major site of epithelial cell cohesion.

21. Adherens Junction
• Cytoplasmic actin filaments bind adherens junctions.
• Homophilic interactions between densely clustered E-
cadherens (the epithelial transmembranic adhesive protein)
bind adjacent cells together at adherens junctions.
• β- catenin(cytoplasmic adapter protein) and Plakoglobin
(desmosomal cytoplasmic adapter protein) bind the cytoplasmic
domains of E-cadherin.

22. Adherens Junction
• An another cytoplasmic adapter protein, α-catenin, binds
cadherins to actin filaments and β-catenin to actin filaments.
• Adherens junctions are first connections that are established
between developing sheets of epithelial cells.
• The contact begins when cadherins on the tips of filopodia
engage to the cadherins of another cell.

23. Adherens Junction
• Adherens junctions are a pre requisite for tight junctions that
allow epithelial cells to establish polarity with proteins and lipids
in plasma membranes.
• Zonula adherens is the major site for cell cohesion.
• It stabilizes the surface of epithelia.
• The junctions and polarity determine the orientation of mitotic
spindle and the plane of division . This allows for asymmetrical
division of stem cells (stratified epithelium).

24. Adherens junction
• In mature columnar epithelia a belt –like adherens junction
called zonula adherens encircles the cell near the apical
surface thus maintaining physical integrity of the epithelium.
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26. DESMOSOMES
• Desmos means ‘bound ‘ , Soma means ‘body’.
• It is also called Macula Adherens.
• Provide strong adhesion between the epithelial and
muscle cells.
• These junctions are small disk shaped “spot welds”
between adjacent cells.
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27. Desmosomes
• Ist observed in the spinous layer of epidermis by an
Italian pathologist Giulio Bizzazero.
• Helps to resist shearing force.
• Structure that forms the site of adhesion between
2 cells ,consisting of dense plate in each adjacent cells
seprated by a thin layer of extracellular material.
• Desmosomes link 2 cells together.
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28. Desmosomes
• Human Gingival Keratinocytes (HGK)s are
interconnected on the cell periphery by
Desmosomes.
• Consist of two dense attachment plaques into
which tonofibrils insert and an intermediate,
electron dense line in the extracellular
compartment.
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29. Desmosomes
• Cellular adhesions at desmosomes are mediated by
transmembrane proteins:
• Desmogleins
• Desmocollins.
• Plakoglobin also called gamma- catenin.
• Molecular composition of desmosomes vary in particular
tissues
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30. Desmosomes
• Desmosomes are site for attachment, structural ability of
epithelium linking cytoskeletal structures of two cells.
• Desmoglein -2 and desmocollin -2 are found in most of the
desmosomes.
• The devlopment of animal tissues depends on desmosomes &
their constituents proteins.
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32. GAP JUNCTIONS
• Gap junctions are plaque that contain large intercellular
channels that connect the cytoplasm of a pair of cells.
• Half channels in each membrane are called connexons.
• Connexons consists of six protein subunits, called
connexins.
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33. Gap Junctions
• Connexin are named by their molecular weight.
• Found exclusively in chordates.
• Most connexons pair with identical connexons on
the partner cell to form homotypic gap junctions.
• Gap junction communication is conditional
• It depends on:
• Number of channels
• Fraction that are open or closed
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34. Gap Junctions
• Plants lacks gap junctions
• Cells in plant tissues maintain continuity
through plasmodesmata.
• Molecules smaller than 1kd diffuse freely
through plasmodesmata.
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36. Gap Junctions
• Oleamide- fatty acid amide produced by the brain , blocks gap
junction and induce sleep in animals.
• Gap junctions allow osteocytes to maintain cellular supply line
to acquire nutrients from distant blood vessels.
• White blood cells may also form transient gap junctions with
endothelial cells.
• Cells in most metazoans communicate by gap junctions.
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37. Gap Junctions
• Mutations in connexins genes cause human
disease.
• Recessive mutation in the connexin -26 gene
are most common cause of human Deafness.
• Mutation in connexin-32 gene causes
degeneration of myelin sheets around axons.
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38. HEMIDESMOSOMES
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Basal Cells
Tonofilaments
Lamina lucida
Lamina densa
Anchoring
filaments
Anchoring fibrils
Type IV
collagen
Proteoglycans
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Hemidesmosomes

39. HEMIDESMOSOMES
• Hemidesmosomes are adhesive
junction that link cytoplasmic
filaments to basal lamina.
• Adhesion to extracellular
matrix is different from
intercellular adhesion
because integrins provide
transmembrane link between
cytoskeleton and extracellular
matrix.
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40. Contd…
• Two transmembrane proteins mainly found in hemidemosomes
are α6β4 integrin and type XVII collagen.
• Outside the cell α6β4 integrin binds to laminin-5 in basal
lamina.
• The extracellular collagen triple helix forms anchors filaments
between membrane and basal lamina.
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41. Contd…
• STRUCTURE OF HEMIDESMOSOME:
– Adhesive protein – INTEGRIN
– Cytoplasmic proteins – PECTIN, BP 180
– Cytoskeletal element - INTERMEDIATE
FILAMENTS
– Target molecule - LAMININ.
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42. CELLULAR ADHESION
PRINCIPLES OF CELLULAR ADHESION
1. First principle of adhesion
• Cells define their capacity for adhesive interactions by selectively
expressing plasma membrane receptors with limited ligand
binding activity.
• For example: Endothelial cells produce E – selectin only when
stimulated by inflammatory hormones
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43. Contd…
2. Second principle of adhesion
• Many adhesion proteins bind one main ligand and many ligands
bind a single type of receptor, for example Most cadherins bind to
themselves, such homophilic interactions require Ca+2 ions.
3. Third principle of adhesion
• It states that cell modulate adhesion by controlling the surface
density, state of aggregation and state of activation of their
adhesion receptors.
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44. CADHERIN FAMILY OF ADHESION
RECEPTORS
• Cadherins name is derived from calcium dependent adhesion
protein.
• Homophilic interactions of cadherins link epithelial and muscle
cells to adjacent cells at specialized junctions called adherens
junctions and desmosomes.
• The cytoplasmic domains of cadherin junctions interact with
actin filaments to maintain physical integrity of tissues.
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45. Contd…
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Structural
Hallmark
of
Cadherin
family is
CAD
domain

46. Cadherins are named according to their location or cells to
which they are attached. for eg:
•Epithelial tissue -E-cadherin
•Nervous tissue - N-cadherin
•Placenta- P-cadherin
• osteoblasts- O-cadherin
•Kidney-K cadherin
•muscle -M-cadherin
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47. • Integrins are the main cellular receptors for extra cellular
matrix.
• Integrins tend to be more promiscous than most adhesion
receptors as some bind to several protein ligands & many
matrix molecule bind to 1 integrin.
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48. SUMMARY
• Intercellular junctions are fundamental to the interactions
between cells.
• Mucosal barrier integrity is maintained by the physical
interactions of intercellular junctional molecules on
opposing epithelial cells.
• In the heart, cell junctions form the low-resistance
pathways for rapid impulse conduction and propagation,
enabling synchronous stimulation of myocyte
contraction.
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49. SUMMARY
• In kidney, cell junctions help to maintain concentrations
of fluid creating a balance between osmotic gradients.
• By means of these junctions, the activities of the
individual cells that make up tissues are co-ordinated,
enabling each tissue system to function as an integrated
whole.
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