HUMAN ANATOMY AND PHYSIOLOGY - I

CELLULAR LEVEL OF ORGANIZATION

CELL JUNCTIONS

Ms. K. K. Sneha
Assistant Professor
Department of Pharmacology
JKKNCP
 DEFINITION AND CLASSIFICATION
• 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 junctions are classified into three types:
1. Occluding junctions
2. Communicating junctions
3. Anchoring junctions
 OCCLUDING JUNCTION
• Cell junctions which prevent intercellular exchange of substances are
called occluding junctions, i.e. these junctions prevent the movement
of ions and molecules from one cell to another cell.
TIGHT JUNCTION:
• It is the intercellular occluding junction that prevents the passage of
large molecules. It is also called zonula occludens. It is the region
where the cell membranes of the adjacent cells fuse together firmly.
This type of junction is present in the apical margins of epithelial
and endothelial cells in intestinal mucosa, wall of renal tubule,
capillary wall and choroid plexus.
Structure of Tight Junction
• It is made up of a ridge which has two halves. One half of the ridge is from
one cell and another half is from the other cell. Both halves of the ridge fuse
with each other very tightly and occupy the space between the two cells.
Each half of the ridge consists of tight junction strands.
• Proteins involved in the formation of tight junctions are classified into 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 ZO-1, 2, 3.
• 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.
Functions of Tight Junction:
1. Strength and stability: The tight junction holds the neighboring
cells of the tissues firmly and thus provides strength and stability to
the tissues.
2. Selective permeability (gate function): The tight junction forms a
selective barrier for small molecules and a total barrier for large
molecules.
Eg: In the epithelial and endothelial cells, tight junction is the most
apical intercellular junction, which functions as selective
(semipermeable) diffusion barriers between the neighboring cells. This
function is called barrier or gate function. Barrier function of tight
junction regulates the interchange of ions, water and varieties of
macromolecules between the cells. The magnitude of this function
varies in different tissues. In some epithelial cells, few substances pass
through the tight junction (by diffusion or active transport). In other
cells, no substance passes through the tight junction.
3. 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. Because of this function, the tight junction is
sometimes referred as impermeable junction.
4. 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.
5. Blood-brain barrier: Tight junction in the brain capillaries forms the
blood-brain barrier, which prevents the entrance of many substances from
capillary blood into brain tissues. Only lipid-soluble substances like drugs
and steroid hormones can pass through the blood-brain barrier.
 COMMUNICATING JUNCTIONS
• Cell junctions which permit the intercellular exchange of substances
are called communicating junctions, i.e. these junctions permit the
movement of ions and molecules from one cell to another cell.
• Gap junction and chemical synapse are the communicating
junctions.
GAP JUNCTION:
• It is the intercellular junction that allows passage of ions and smaller
molecules between the cells. It is also called nexus. It is present in
heart, basal part of epithelial cells of intestinal mucosa, etc.
Structure of Gap Junction
• Membranes of the two adjacent cells lie very close to each other and
the intercellular space is reduced from the usual size of 2.5 to 3 nm.
• Cytoplasm of the two cells is connected by the channels formed by the
membranes of both cells. So, the molecules move from one cell to
another cell directly through these channels, without having contact
with extracellular fluid (ECF).
• Each channel consists of two halves. Each half belongs to one of the
two adjacent cells. Each half of the channel is surrounded by 6
subunits of proteins which are called connexins or connexons.
Functions of Gap Junction;
1. 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.
2. It helps in the exchange of chemical messengers between the cells.
3. It helps in rapid propagation of action potential from one cell to
another cell.
Regulation of the Diameter of Channels in Gap Junction:
• In the gap junctions, the diameter of each channel is regulated by the
intracellular calcium ions.
• When the concentration of intracellular calcium ion increases, the
protein subunits of connexin surrounding the channel come close to
each other by sliding. Thus, the diameter of the channel decreases.
• The diameter of the channel is also regulated by pH, electrical
potential, hormones or neurotransmitter.
Chemical Synapse
• It is the junction between a nerve fiber and a muscle fiber or between
two nerve fibers, through which the signals are transmitted by the
release of chemical transmitter.
• In the chemical synapse, there is no continuity between the two
neurons because of the presence of a space called synaptic cleft
between the two neurons.
• Action potential reaching the presynaptic terminal causes release of
neurotransmitter substance from the vesicles of this terminal.
• Neurotransmitter reaches the postsynaptic neuron through synaptic
cleft and causes the production of potential change.
Anchoring junctions
• Anchoring junctions provide strength to the cells by acting like
mechanical attachments, i.e. these junctions provide firm structural
attachment between two cells or between a cell and the extracellular
matrix.
• Anchoring junctions are responsible for the structural integrity of the
tissues and are present in the tissues like heart muscle and epidermis of
skin, which are subjected to severe mechanical stress.
• The firm attachment between two cells or between a cell and the
extracellular matrix is provided by either actin filaments or the
intermediate filaments.
Anchoring junctions are classified into four types:
1. Actin filament attachment
i. Adherens junction (cell to cell)
ii. Focal adhesion (cell to matrix)
2. Intermediate filament attachment
i. Desmosome (cell to cell)
ii. Hemidesmosome (cell to matrix)
Adherens Junction
• It is the cell to cell junction, which connects the actin filaments of one
cell to those of another cell.
• In some places like epithelial linings, this junction forms a continuous
adhesion (zonula adherens) just below the tight junctions.
• In adherens junction, the membranes of the adjacent cells are held
together by some transmembrane proteins called cadherins.
• It provides strong mechanical attachments of the adjacent cells.
• It is present in the intercalated disks between the branches of cardiac
muscles. During the contractions and relaxation of heart, the cardiac
muscle fibers are held together tightly by means of this junction.
• The adherens junction present in epidermis helps the skin to withstand
the mechanical stress.
Focal adhesion
• It 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.
Desmosome
• It is a cell to cell junction, where the intermediate filaments connect
two adjacent cells.
• It is also called macula adherens.
• The membranes of two adjacent cells, which oppose each other, are
thickened and become spot-like patches.
• Intermediate filaments are attached with the thickened patches.
• Some of these filaments are parallel to the membrane and others are
arranged in radiating fashion.
• It function like tight junctions.
• The transmembrane proteins involved in desmosome are mainly
cadherins.
Hemidesmosome
• It is a cell to matrix junction, which connects the intermediate
filaments of the cell to the extracellular matrix.
• This type of cell junction is like half desmosome and the thickening of
membrane of only one cell occurs. So, this is known as
hemidesmosome or half desmosome.
• Mostly, the hemidesmosome connects the cells with their basal lamina.
• The proteins involved in this are integrins.