2. Definition and Classification of cell
junction
• Cell junction is the connection between the neighboring
cells or the contact between the cell and extracellular
matrix.
• It is also called membrane junction.
• Cell junction are classified into three types
– Occluding junction
– Communicating junction
– Anchoring junction.
3. Cell Adhesion Molecules
(CAMs)
• Important cell surface proteins molecules
promoting cell–cell and cell–matrix
interactions.
• Important for many normal biological
processes - embryonic cell migration,
immune system functions, wound healing.
• Involved in intracellular signaling
pathways (primarily for cell
death/survival, secretion etc.)
4. Cell Adhesion Molecules
(CAMs)
• Express 3 major domains:
• The extracellular domain allows one CAM to
bind to another on an adjacent cell.
• The transmembrane domain links the CAM to
the plasma membrane through hydrophobic
forces.
• The cytoplasmic domain is directly connected
to the cytoskeleton by linker proteins.
6. • Interactions between CAMs can be
mediated by :
Binding of an
adhesion
molecule on one
cell to the same
adhesion
molecule on a
second cell
Cadherin-
cadherin
An adhesion
molecule on one
cell type binds to
a different type of
cell adhesion
molecule on a
second cell
Selectins – mucins
The linker
molecule in most
cases is Laminin, a
family of large
cross shaped
molecules with
multiple receptor
domains.
7. • These cell adhesion molecules can be
divided into 4 major families
– The Cadherin Superfamily
– The Selectins
– The Immunoglobulin Superfamily and
– The Integrins
8. THE CADHERIN SUPERFAMILY
• Cadherins are the most prevalent CAMs in
vertebrates.
• 125 kD transmembrane glycoproteins - mediate
intercellular adhesion in epithelial and
endothelial cells by Ca2+ dependent homophilic
adhesion.
• Primarily link epithelial and muscle cells to their
neighbors- Form desmosomes and adherens junctions
• Play critical role during development (cell
sorting).
• Do not interact with extracellular matrix.
9. THE CADHERIN SUPERFAMILY
• Contain a short transmembrane
domain and a relatively long
extracellular domain containing
four cadherin repeats (EC1-EC4),
each of which contains calcium
binding sequences
• Cadherins interact with specific
cytoplasmic proteins, e.g., catenins
(α, β and γ), as a means of being
linked to the actin cytoskeleton.
• The binding of cadherins to the
catenins is crucial for cadherin
function.
10. THE SELECTINS
• Structural features of selectins include:
1. NH2-terminal C-type Ca2+ dependent
lectin like binding domain, which
determines the ability of each selectin to
bind to specific carbohydrate ligands.
2. An epidermal growth factor-like region.
3. A number of repeat sequences.
4. A membrane-spanning region and a short
cytoplasmic region
12. Immunoglobulin Superfamily
Molecules
• Consists of more than 25 molecules.
• Important ones being:
– Intracellular adhesion molecule 1(ICAM1;
CD54)
– Intercellular adhesion molecule 2 (ICAM2),
– Vascular cell adhesion molecule1 (VCAM1;
CD106),
– Platelet endothelial cell adhesion molecule 1
(PECAM 1; CD31) and
– The Mucosal Addressin Cell Adhesion
molecule 1 (MAdCAM1).
13. THE INTEGRINS
• Fifteen different α and eight
different β subunits give rise to
over twenty different
heterodimeric combinations at
cell surfaces.
• Bind epithelial and muscle cells
to laminin in the basal lamina.
• Allow platelets to stick to
exposed collagen in a damaged
blood vessel.
• Allow fibroblasts and white blood
cells to adhere to fibronectin and
collagen as they move.
15. OCCLUDING JUNCTION
• A cell-cell junction that seals cells together in an epithelium in a way
that prevents even small molecules from leaking from one side of the
sheet to the other.
• Tight Junction : Tight Junction- occluding junctions / zonulae
occludens - zonula occludens) are the closely associated areas of
two cells whose membranes join together forming a virtually
impermeable barrier to fluid.
• A type of junctional complex present only in vertebrates.
• Consist of linear array of several integral proteins.
• Junctional proteins occludins and claudins & members of IG
superfamily are transmembrane proteins.
16. Function of Tight Junction
1. Strength and stability
2. Selective permeable for ions.
3. Fencing function
4. Maintenance of cell polarity
5. Blood-brain barrier
6. Claudin -16 in Thick Junctions of
Ascending Loop of henle.
7. Claudin- 15 Permeability of cations /
anions.
17. ADHERING JUNCTIONS
• Desmosome- Connects intermediate
filament of one cell with other cells.
• Claudin
• Hemidesmosome
• Desmoplakin is essential for normal
desmosomal adhesion.
18. COMMUNICATING JUNCTION
• Cell junction which permits the
intercellular exchange of substance
are called communicating junction,
these junctions permit the movement
of ions and molecules from one cell to
another cell.
a- Gap junction
b- Chemical synapse
19. GAP JUNCTION
• Gap junctions are clusters of intercellular
channels that allow direct diffusion of ions
and small molecules between adjacent
cells.
• At gap junctions, the intercellular space
narrows from 25 nm to 3 nm.
20. GAP JUNCTION
• Gap junctions were first discovered in
myocardium and nerve because of their
properties of electrical transmission
between adjacent cells (Weidmann 1952;
Furshpan and Potter 1957).
21. GAP JUNCTION
• Low resistance intercellular junction that allows
passage of ions and smaller molecules between
the cells.
• It presents in heart, basal part of epithelial cell of
intestinal mucosa, etc.
• Junctional unit-Connexons- 6 connexins
• Connexon of one cell have alignment with
connexon of other cells.
22. GAP JUNCTION
• Electron microscopy of gap junctions joining adjacent hepatocytes in
the mouse. The gap junction (GJ) is seen as an area of close plasma
membrane apposition
23. FUNCTION OF GAP
JUNCTION
1. Channel passage the substance has molecular
weight less than 1000.
2. Exchange of chemical messenger between cells
3. Rapid propagation of action potential from one
cell to another cell.
24. DESMOSOMES
• Also known as macula adherens is a cell structure
specialized for cell-to-cell adhesion.
• Are molecular complexes of cell adhesion proteins
and linking proteins that attach the cell surface
adhesion proteins to intracellular keratin
cytoskeletal filaments.
• The cell adhesion proteins of the desmosome,
desmoglein and desmocollin, are members of the
cadherin family.
26. HEMIDESMOSOMES
• Hemidesmosomes look like half-
desmosomes that attach cells to the
underlying basal lamina.
• Rather than using desmogleins,
hemidesmosomes use desmopenetrin cell
adhesion proteins, which are members of
Integrin family.
27. CHEMICAL SYNAPSE
• Chemical synapse is the junction between
a nerve fibre and a muscle fiber or between
two nerve fibre, through which signals
transmitted by the release of chemical
transmitter.
30. ANCHORING JUNCTION
• Anchoring junction are the junction ,which
provides strength to the cell by acting like
mechanical attachment.
• These junctions provide firm structural
attachment between two cells or between a cell
and extracellular matrix
• Anchoring junction are responsible for structural
integrity of the tissue.
31. Various cell junctions found in a vertebrate epithelial cell,
classified according to their primary functions