Cell Junctions & Cell Communication Presented By :

Dr. Tareq Abu-Libdeh

➢ Cell Junctions

▪ Definition & classification:

Cell junction is the connection between adjacent cells
or between the cell and extracellular matrix
(basement membrane )
1. cell- cell adhesion
2. cell- matrix adhesion (epithelial tissue only)

➢ Cell membrane proteins

▪ They are of two types; either peripheral or integral
1. Peripheral: are temporary attached to the cell membrane.
Found on the outside & inside surfaces of the cell membrane. (extrinsic proteins)

2. Integral ( interensic proteins) : are permanently attached to the membrane.

They are of two types :
-Transmembrane proteins that span across the cell membrane
-Monotopic proteins attached to only one side of the membrane
and do not span across the cell membrane .
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
➢ Function of integral membrane proteins
1. Junctions – Serve to connect and join the cells together
2. Enzymes – Fixing to membranes to perform a localized metabolic pathways
3. Transport – Responsible for facilitated diffusion and active transport
4. Recognition – May function as markers for cellular identification
5. Anchorage – Attachment points for cytoskeleton and extracellular matrix
6. Transduction – Function as receptors for peptide hormones

Function of cell membrane integral proteins

➢ Function of cell- cell junctions (adhesions)
1. Communication between adjacent cells.
2. Support & reduce stress placed upon cells.
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
Cell adhesion molecules (CAMs)
A group of cell proteins (glycoproteins) located on the
cell surface (transmembrane) & involved in binding of
the cell with neighbor cells or with the extracellular
matrix in a process called cell adhesion

➢ Cell-cell junctions (Adhesions)

Represent the mechanism behind how cells connect &
interact with each other, this is achieved by molecules
of CAMs present at the surface of both cells.
Cell junctions is vital for multicellular structural maintenance

Inside the cell there are 3 types of cytoskeletons : actin filament , intermediate filament & Microtubules

Theses cytoskeleton is responsible for support, contraction, motility ,movement of organelles,

organization of the cytoplasm & polarity of the cell
➢ Cell Adhesion Molecules (CAMs) cont.
✓ Are Proteins located on the cell surface (typically trans- membrane proteins)
✓ They help in attaching cells e each other & e their EC matrix, also Play a role in immunity &
cancer metastasis, wound healing, and cell tissue organ development
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh

▪ CAM molecule composed of 3 major domains:

1. The extracellular domain: allows one
CAM to bind with another CAM on an
adjacent cell.
2. The transmembrane domain: links the
CAM to the plasma membrane through
hydrophobic forces.
3. The cytoplasmic domain: is directly
connected to the cytoskeleton
by linker proteins.

CAMs can be divided into 4 major protein families:

❖ How CAM molecules bind with each other ?
▪ When CAMs of the same kind bind together
Is called (homophilic binding)
▪ When CAMs of different types bind
together or with the ECM is called
(heterophilic binding)
▪ Through The linker molecule when the
two CAMs are different. Laminin (linker
molecule) is a family of large cross shaped
molecules with multiple receptor domains

Interactions between CAMs can be mediated by :

Binding of CAM on one cell to CAM on one cell type binds to a The linker molecule in
the same CAM on a second cell different type of CAM on a most cases is Laminin,
second cell a family of large cross
Cadherin - Cadherin
shaped molecules
Selectins – Mucins
with multiple
receptor domains.
CAM binds to EC matrix
is also a heterophilic binding
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh

❖ CAMs Families: Only Integrins binds cell to the extracellular matrix ( basement membrane),
while selectins, cadherins , and IgSF members are associated with cell- cell adhesion.

Epithelial Cells are polar in nature because :

1. Epithelial Cells rest on basal lamina
& have apical & lateral borders
2. Adjacent cells attach with CAMs & intercellular junctions
3. CAMs Support & hold the tissues together

A. Cell- Cell junctions

▪ Cell junctions consist of multi-protein complexes
▪ They are particularly plentiful in epithelial tissue
▪ Types of cell junctions :

1. Occluding/Tight junctions:
Seal cells Together like a sheet to prevent flow of molecules even water or ions between cells
2. Anchoring junctions:
attach cells & their cytoskeleton to other cells or to ECM provide mechanical support
3. Gap junctions:
allow exchange of chemical / electrical information between adjacent cells
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh

Cell junctions are multi-protein complexes

➢ Types of cell junctions in multicellular organism:

1- Occluding junctions:
✓ Also called tight Junctions / zonula occludens
✓ Seal adjacent epithelial cells & is the most apical type of junctions
✓ Belt-like structure encircle completely the apical cell surface of the epithelial cells
✓ Water & ion molecules cannot pass through that junction
(passaging either through active transport or facilitated diffusion)
✓ The membranes of adjacent cells fuse at the tight junction
✓ completely forming impermeable barrier/diffusin barrier
✓ Proteins forming this junction are occludins and claudins
✓ Need ca to function
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
Functions of Tight Junction

a. Protection: Seals cells thus it creates

barriers to prevent leaks

b. Blood-brain barrier & other barriers in

the body especially in GIT

c. Maintain cell polarity: prevent

membrane proteins of apical surface
from being moved to basolateral
surface to maintain cell receptors &
function

d. Ensure unidirectional transport, the

apical set of transport proteins must
not be allowed to migrate to the
basolateral surface & vice versa

Leaky gut syndrome : is a disease happen when tight junctions between intestinal epithelial cells
(intestinal barrier) become defective
→ abnormal increases in the intestinal permeability
→ leaking of a undigested food particles, toxins & microbes from the lumen into the blood stream
→ digestive disorders and various inflammatory and immune diseases
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
 Most cancers originate from epithelial cells.
 Down regulation of Tight junctions adhesion proteins lead to
tumor dissociation and subsequent metastasis.
 Researchers observed low expression of TJ proteins among highly metastatic cancer cells

2 - Anchoring junctions
✓ Cell – cell: Adherens junction + Desmosome
✓ Cell – matrix: Hemi-desmosome
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
A- Adherens junction/Zonula adherens

• Integral membrane proteins, connect the cell cytoskeleton to another cell

• Encircle the cell, just below ZO, but they don’t seal
• Found in tissues subject to Stretch to resist separation of cells during
contraction (bladder, uterus, skin).
• The opposing plasma membranes has a narrow space in-between
• The cytoplasmic surfaces of adjacent cell membranes at the junction have electron dense
plaques (glycoprotein)
• Proteins forming the Junction are Cadherins, Catenin
• The plaques(catenin) provide attachment for transmembrane protein (cadherins)
and for the fine cytoskeleton filaments (Actin filaments)
• This junction makes the Terminal Web at the apical part of epithelial cells having microvilli
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
B- Desmosomes/Macula adherens
✓ Scattered disc- shaped structures, arranged randomly on the lateral sides of the cells
don't form belt (spot- like)
✓ Disc plaque at the surface of one cell connects with an identical one at the surface of the adjacent cell
✓ Proteins forming the junction of the desmosome are desmoplakin (plaque)
& desmoglein & desmocoline (transmembrane proteins ) ( members of the cadherin family)
✓ Within the cell, the desmoplakin provide insertion to keratin (intermediate cytoskeleton filaments)
✓ Found in tissues to resist high stretch and stress e.g. between cardiac muscles (intercalated discks),
skin, intestine. They are stronger than adherens junction

Pemphigus vulgaris
Due defect in desmoglin of Epidermis of skin
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
C- Hemidesmosomes:
Half desmosome (cell – basal lamina /ECM)
✓ At the base of epithelial cells
✓ Bind epithelial cells to basal lamina
✓ The transmembrane protein is integrins protein
✓ Plaques provide attachment for keratin filaments
✓ integrin molecules connect to laminin of basal lamina in turn connect e collagen in ECM
→ cell-matrix adhesion (bullous pemphigoid)

Bullous pemphigoid (BP)

is a chronic blistering of the skin.
It ranges from mildly itchy welts to severe blisters and infection,
and may affect a small area of the body or be widespread.
The vast majority of those affected are elderly,
but it has been seen at all ages.

❖ Function of anchoring junctions

▪ Stabilize cells against mechanical stress
▪ Mechanically attach cells & their cytoskeleton to their neighbor cells or to the extra cellular matrix
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
3- Gap junction (GJ)
✓ Transmembrane proteins form intercellular channels that allow
direct transfer of ions, small molecules, electric impulses
between cytoplasm of adjacent cells

✓ This type of junction makes the cells chemically or electrically coupled

✓ This type of junction is important in heart muscle cells.

✓ It provides low resistance ions pathways through GJ allowing

the cell to contract

The protein subunit forming the junction is called Connexin

• Each channel called Connexon is formed by

6 Connexins subunits which span the lipid
bilayer of the cell membrane (hydrophobic)
• The connexons tubes of 2 cells join together
to make a GJ
• GJ tend to close by high concentration of Ca+
ions or low pH.
• The closing of the GJ serves to seal normal cells
from traumatized or dying neighbors
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh
➢ Electrical & Chemical synapses
Synapse is a type of GJ where information is transmitted between adjacent cells.
There are 2 types:
A. Electrical synapse: is a GJ which has channel proteins connecting the adjacent cells.
The signal in electric synapse can travel faster .
▪ Found between: cardiac muscles (intercalated discs) , and in
synapses between neurons involved in reflexes in nervous
system & between smooth muscle cells
▪ Intercalated discs: contain both GJs & Desmosomes to
allow flow of ions from one cell to another
→ spread of action potential & to hold cells together
B- chemical synapse (Signal relaying junction)
▪ Junction between a nerve fiber and a muscle fiber
(motor end plate) or between two neurons
▪ The neuron transmitting the signal is called
presynaptic neuron.
▪ Synaptic vesicles containing neurotransmitters are
found in the presynaptic neurons
▪ These neurotransmitters will be released into the
synaptic cleft
(space between pre & postsynaptic membranes).
▪ Neurotransmitter will bind to protein receptors on
the postsynaptic membrane
 Cell Junctions & Cell Communication Presented By :
Dr. Tareq Abu-Libdeh

Gap junctions also found between many cells

e.g. osteocytes, astrocytes, endocrine cells , smooth muscles

Cancer cells don’t have gap junctions

so that they fail to transfer their mitotic activity to each other
which may explain their uncontrolled growth

Changes in the number and distribution of gap junctions has been reported in many
cardiac diseases e.g. arrhythmias