Cell junctions connect neighboring cells and mediate cell-cell and cell-matrix interactions. They are classified as tight junctions, gap junctions, and anchoring junctions. Tight junctions form selective barriers between cells, while gap junctions allow small molecules to pass directly between cells. Anchoring junctions like adherens junctions and desmosomes provide strength through connections to cytoskeletal proteins. Cell adhesion molecules like integrins, cadherins, and selectins are involved in cell binding and play roles in processes like differentiation, migration, and survival.

1. INTERCELLULAR
JUNCTIONS
Dr. JILSHA

2. OBJECTIVES
To get a better understanding on
 Definition of cell junctions
 History
 Classification
 Types, their functions, proteins involved
and applied physiology
 Cell adhesion molecules (CAMs)
 Types of CAMs and functions.
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3. INTRODUCTION
 The cell membranes of the neighboring cells are
connected with one another through the
intercellular junctions or the junctional complexes.
 Also called as membrane junctions.
 They mediate two types of interactions :
 Cell to cell
 Cell to extracellular matrix
 Abundant in epithelial tissues.

4. ▪ On the molecular level, intercellular
junctions consists of three components :
▫ Transmembrane adhesive protein
▫ Cytoplasmic adapter protein
▫ Cytoskeletal filament
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5. HISTORY
▪ Cell–cell junctions in the mammary gland were first
described in detail by Dorothy Pitelka in a series of
classic electron micrographs, both transmission and
freeze fracture.
▪
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6. CLASSIFICATION
▪ TIGHT JUNCTIONS
▪ GAP JUNCTIONS
▪ ANCHORING JUNCTIONS
▫ CELL TO CELL
▫ Adherens junctions
▫ Desmosomes
▫ CELL TO MATRIX
▫ Focal adhesion
▫ Hemidesmosomes
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8. TIGHT JUNCTIONS
▪ Also called as zonula occludens or the occluding
zone.
▪ Typically located towards the apical region of the
cells.
▪ The outer layer of the CM of the neighboring cells
fuse with each other that obliterates the
intercellular space close to their apical margin.
▪ Made up of ridges, half of which is contributed by
both neighboring cells and each half is bound tightly
to each other.
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9. ▪ Form barrier to the movement of ions and other
solutes from the lumen into the interstitial space
and between cells.
▪ Tight junctions permit the passage of some ions
and solute in between adjacent cells (paracellular
pathway) by means of leaky ion and water channels
and the degree of this “leakiness” varies,
depending in part on the protein makeup of the
tight junction.
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10. ▪ Characteristically seen along the apical
margins of cells in epithelium such as the
intestinal mucosa, the walls of the renal
tubules, and the choroid plexus.
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12. PROTEINS OF TIGHT JUNCTIONS
▪ Two types :
1. Tight junction membrane proteins or integral
membrane proteins, such as occludin, claudin
and junctional adhesion molecules (JAMs).
2. Scaffold (framework or platform) proteins or
peripheral membrane proteins or cytoplasmic
plaque proteins such as cingulin, symplekin and
ZO1, 2, 3.
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13. ▪ Tight junction membrane protein molecules are
anchored in the strands of the ridge and attach
with their counterparts of neighboring cell, so that
both the cells are held together.
▪ The scaffold (platform) proteins are attached
with the tight junction membrane proteins and
strengthen the anchoring in the ridges.
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15. FUNCTIONS OF TIGHT JUNCTIONS
▪ STRENGTH AND STABILITY
▫ The tight junction holds the neighboring
cells of the tissues firmly and thus provides
strength and stability to the tissues.
 SELECTIVE PERMEABILITY
 The tight junction forms a selective barrier
for small molecules and a total barrier for
large molecules.
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16. ▪ FENCING FUNCTION
▫ Tight junction prevents the lateral
movement of proteins (integral
membrane proteins) and lipids in cell
membrane and thus acts as a fence.
▫ The fencing function maintains the
different composition of proteins and
lipids between the apical and
basolateral plasma membrane domains.
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17. ▪ MAINTENANCE OF CELL POLARITY
▫ Fencing function of the tight junction
maintains the cell polarity by keeping
the proteins in the apical region of the
cell membrane.
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18. ▪ In the brain, tight junctions between the
endothelial cells of cerebral blood vessels
contribute to the effectiveness of BBB.
▪ In the ciliary bodies, they form blood – aqueous
barrier between the cells of inner non –
pigmented epithelium.
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19. APPLIED PHYSIOLOGY
▪ Diseases caused by mutation of genes
encoding proteins of tight junction:
▫ Hereditary deafness
▫ Ichthyosis
▫ Sclerosing cholangitis
▫ Hereditary hypomagnesemia
▫ Synovial sarcoma
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20. GAP JUNCTIONS
▪ Gap junction is the intercellular junction
that allows passage of ions and smaller
molecules between the cells.
▪ Gap junctions are called nexus between
the cells at which the intercellular space is
narrowed from 25 nm to 3 nm.
▪
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21. ▪ Made up of transmembrane proteins known as
connexons.
▪ The connexons from the membrane of two
adjacent cells are lined up with one another.
▪ Each connexon is formed by six identical protein
subunits called connexins.
▪ Connexin surrounds an aqueous channel.
▪ When connexon of adjacent cells are aligned, the
aqueous channels of both cell membranes
become a continuous one.
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22. ▪ This allows substances of adjacent two cells to
pass through the channel without passing through
the ECF.
▪ The diameter of each channel is regulated by
intracellular Ca2+,pH and voltage.
▪ As connexons keep the adjacent cell membranes
at a fixed gap, the junction is named as “gap
junctions”.
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25. TIGHT JUNCTION vs GAP JUNCTION
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26. FUNCTIONS OF GAP JUNCTIONS
▪ Diameter of the channel in the gap junction is
about 1.5 to 3 nm. So, the channel permits the
passage of glucose, amino acids, ions and other
substances, which have a molecular weight less
than 1,000.
▪ It helps in the exchange of chemical
messengers and hormones between the cell.
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27. ▪ Electrical synapses:
▫ As the pores of gap junction are larger than
ligand-gated or voltage-gated channels,
passage of substances is easier through them.
▫ Gap junctions easily allow ions to pass through
and serve as electrical synapses, as they
permit rapid propagation of electrical activity
from cell to cell.
▫ Therefore, tissues with gap junctions between
cells behave as physiological syncytium.
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28. APPLIED PHYSIOLOGY
▪ In humans, there are about 20 different genes
that code for connexin proteins. Mutation of
these genes results in diseases that are
specific for tissues.
▪ Few examples are :
▫ Deafness
▫ Keratoderma
▫ Cataract
▫ Charcot MarieTooth disease
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29. ANCHORING JUNCTIONS
▪ Anchoring junctions are the junctions, which
provide strength to the cells by acting like
mechanical attachments.
▪ Anchoring junctions are responsible for the
structural integrity of the tissues.
▪ Present in the tissues like heart muscle and
epidermis of skin, which are subjected to severe
mechanical stress.
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30. ▪ The firm attachment between two cells or between
a cell and the extracellular matrix is provided by
either actin filaments or the intermediate filaments.
▪ Depending upon this, anchoring junctions are
classified into four types:
▫ 1. Actin filament attachment
▫ Adherens junction (cell to cell)
▫ Focal adhesion (cell to matrix)
▫ 2. Intermediate filament attachment
▫ Desmosome (cell to cell)
▫ Hemidesmosome (cell to matrix)
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32. ADHERENS JUNCTION
▪ Also called as zonula adherens.
▪ Cell to cell junction, which connects the actin filaments
of one cell to those of another cell.
▪ The membranes of the adjacent cells are held together
by transmembrane proteins called cadherins.
▪ Adherens junction is present in the intercalated disks
between the branches of cardiac muscles.
▪ The adherens junction present in epidermis helps the
skin to withstand the mechanical stress.
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34. FOCAL ADHESION
▪ Focal adhesion is the cell to matrix junctions,
which connects the actin filaments of the cell to
the extracellular matrix.
▪ In epithelia of various organs, this junction
connects the cells with their basal lamina.
▪ The transmembrane proteins, which hold the
cell membrane and the matrix are called
integrins.
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35. DESMOSOME
▪ Desmosome is a cell to cell junction, where the
intermediate filaments connect two adjacent cells.
▪ Also called as macula adherens.
▪ Characterized by focal thickening of two adjacent
cell membranes.
▪ The thickened area is the presence of dense layer of
proteins on the cytoplasmic surface of the
membrane.
▪ Thickened area of two sides is separated by a gap of
25 nm.
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36. ▪ Intermediate filaments from cytosol are
attached to the thickened areas.
▪ The transmembrane proteins involved in
desmosome are mainly cadherins.
▪
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38. HEMIDESMOSOME
▪ Hemidesmosome is a cell to matrix junction,
which connects the intermediate filaments of the
cell to the extracellular matrix.
▪ In appearance, they look like half of
desmosomes, and therefore are called
hemidesmosome.
▪ Thickening of membrane occurs in only one cell.
▪ The proteins involved in this are integrins.
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40. APPLIED PHYSIOLOGY
▪ Dysfunction of adherens junction and focal
junction in colon due to mutation of proteins
results in colon cancer.
▪ Dysfunction of desmosome causes bullous
pemphigoid.
▪ Dysfunction of hemidesmosome also causes
bullous pemphigoid. The patients develop
antibodies against integrins.
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41. SUMMARY
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42. CELL ADHESION MOLECULES
▪ Cells are attached to each other and to the basal
lamina by cell adhesion molecules (CAMs) that are
present abundantly at intercellular connections.
▪ By their property of adhesions between the cells,
they provide stability to the tissue.
▪ Involved in stimulating signals that regulate cell
differentiation, cell cycle, cell migration and cell
survival.
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43. SYSTEMS OF BINDING
▪ Extracellular and intracellular bindings.
▪ EXTRACELLULAR :
▫ Many of CAMs bind to membrane proteins
called laminins.
▫ Laminins are cross-shaped large membrane
molecules that have multiple receptor domains
on the extracellular matrix.
▫ CAMs bind to these extracellular receptor
domains.
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44. ▪ INTRACELLULAR
▫ Cell adhesion molecules (CAMs) pass
through the cell membrane to expose
into the interior of the cell and attach
with the cytoskeleton inside the cell.
▫ This intracellular binding of CAMs
with cytoskeletal structures enhances
strength of cell adhesions
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45. NATURE OF BINDING
▪ Homophilic and Heterophilic bindings.
▪ HOMOPHILIC BINDING
▫ In homophilic bindings, CAMs attach with
similar molecules present on the other
cells.
▪ HETEROPHILIC BINDING
▫ In heterophilic bindings, CAMs attach with
different molecules of other cells.
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46. TYPES OF CAMs
▪ Broadly categorized into four varieties:
▫ Integrins
▫ IgG superfamily proteins
▫ cadherins
▫ Selectins
▪
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47. INTEGRINS
▪ Heterodimeric glycoproteins that bind to
various receptors.
▪ Two types : alpha and beta.
▪ Forms focal adhesion and
hemidesmosomes thus participating in cell to
cell adhesion.
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49. IgG SUPERFAMILY
▪ Calcium – independent transmembrane
glycoproteins.
▪ Members : ICAM, VCAM – 1, PECAM -1,
NCAM.
▪ Both homophilic and heterophilic binding.
▪ Involved in recognition, binding or adhesion
process of cells.
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50. CADHERINS
▪ Calcium-dependent adhesion molecules.
▪ Exhibit homophilic binding.
▪ These CAMs form adherens junction and
desomosome.
▪ Subclasses include : Neural, Placental and
Epithelial cadherin.
▪ Failure of cadherin mediated cell to cell adhesion
– breast cancer.
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51. SELECTINS
▪ Divalent cation dependent glycoproteins.
▪ They have carbohydrate binding domains.
▪ Members : Endothelial selectin, Leukocycte
selectin, Platelet selectin.
▪ Plays important role in host defense
mechanisms.
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53. FUNCTIONS OF CAMs
▪ They zip cell to cell. Cell adherence is
strengthened by CAMs.
▪ For their attachment with cytoskeleton, they play
role in cell movement.
▪ Cellular signals are transmitted out of the cell or
extracellular signals are transmitted into the cell
via CAMs.
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54. ▪ They play significant role in inflammation
and wound healing.
▪ CAMs prevent apoptosis. Loss of cellular
contact from extracellular matrix due to
defects in CAMs hastens the process of
apoptosis.
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