BMS 251

GENERAL PRINCIPLES OF PHYSIOLOGY, EXCITABLE

TISSUES AND AUTONOMIC NERVEOUS SYSTEM (ANS)

TOPIC
CELL JUNCTIONS

LECTURER

MR EPHRAIM IME EKANEM

DEFINITION
➢ It is the connection between the neighboring cells or the contact between the
cell and extracellular matrix.
➢ It is also called membrane junction.
Types of Cell Junctions
● Occluding junctions
● Communicating junctions
● Anchoring junctions
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.
Example: Tight Junction
Tight Junction: (occluding junctions / zonulae occludens - zonula occludens)
➢ They 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.
➢ It consist of linear array of several integral proteins.
➢ Junctional proteins occludins and claudins & members of immunoglobulin
suprfamily are transmembrane proteins.
➢ Prevent leakage of fluid.
➢ Found in the apical region around the cell's circumference.
➢ It prevent mobility of transmembrane proteins.
➢ It regulate the movement of water and solutes between epithelial layer.
➢ It lines the gastrointestinal tract.
Function of Tight Junction
➢ Strength and stability
➢ Selective permeable for ions.
➢ Fencing function
➢ Maintenance of cell polarity
➢ Blood-brain barrier
APPLIED PHYSIOLOGY
Diseases caused by mutation of genes encoding proteins of tight junction
➢ Sclerosing cholangitis (inflammation of bile duct causing obstruction)
➢ Hereditary hypomagnesemia (low level of magnesium in the blood)
➢ Synovial sarcoma (soft tissue cancer)
➢ Some bacteria and viruses also affect the functions of tight junction.
➢ Hereditary deafness
➢ Ichthyosis (scaly skin)
Communicating Junctions
● Gap Junction
● Chemical Synapse
● Gap Junction
➢ It is characterized by presence of minute tubular passageways.
➢ It provide direct cell to cell communication
➢ Tubular passages is a low resistance intercellular junction that allows passage
of ions and smaller molecules between the cells.
➢ It is a communicating junction.
➢ It is consist of intercellular channels in the plasma membrane of adjacent cells.
➢ Consist of six connexon proteins arranged to form a doughnut shape structure.
➢ It present in heart, basal part of epithelial cell of intestinal mucosa, etc.
➢ It plays role in cardiac muscle contraction.
➢ Helps in signal transfer in brain.
➢ Their size vary in different cells.
➢ 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.
➢ 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).
➢ Connexon of one cell have allignment with connexon of other cells.
Functions of Gap Junction
➢ It helps in the exchange of chemical messengers between the cells
➢ It helps in rapid propagation of action potential from one cell to
another cell.
➢ 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.
Chemical Synapse
➢ Chemical synapse is the junction between a nerve fiber and a muscle
fiber or between two nerve fiber ,through which signals transmitted by
the release of chemical transmitter.
APPLIED PHYSIOLOGY
Mutation in the genes encoding the connexins causes diseases such as:
➢ Deafness.
➢ Keratoderma (thickening of skin on palms and soles).
➢ Cataract (opacity of lens in eye).
➢ Peripheral neuropathy (damage to the nerves of peripheral nervous
system)
➢ Charcot-Marie-Tooth disease (a form of neuropathy)
➢ Heterotaxia (abnormal arrangement of organs or parts of the body in
relation to left-right symmetry).
ANCHORING JUNCTION
➢ Anchoring junction are the junction ,which provides strength to the cell by
acting like mechanical attachment.
➢ These junction provide firm structural attachment between two cells or
between a cell and extracellular matrix.
➢ Anchoring junction are responsible for structural integrity of the tissue.
➢ Cells within tissues anchor to one another and to extracellular fluid.
Types Anchoring Junction
● Desmosomes Junction
● Focal Adhesion
● Hemidesmosomes Junction
● Adherens Junction
Anchoring Junctions
DESMOSOMES
➢ It forms cell to cell junction also known as Maculae adherens.
➢ Intracellular adaptor proteins connect to intermediate filament and form
cytoplasmic plaque.
➢ Cadherin joins the cytoplasmic plaques of two cells.
➢ The gap b/w this junction is 30nm.
➢ They are found in epidermis of skin and muscle tissues.
➢ Adherens junction 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.
➢ In the epithelial linings, this junction forms a continuous adhesion (zonula
adherens) just below the tight junctions.
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.
HEMIDESMOSOMES
➢ It connects cell to extracellular fluid.
➢ It also connect epithelial cells to basement membrane.
➢ Integrins are the linking proteins.
➢ Present in epidermis of skin.
➢ This type of cell junction is like half desmosome and the thickening
of membrane of only one cell occurs.
➢ It is otherwise known as hemidesmosome or half desmosome.
➢ The hemidesmosome connects the cells with their basal lamina.
Hemidesmosomes
ADHERENS JUNCTION
➢ Junctions which form junction b/w cell to cell.
➢ Also known as Zonulae adherens.
➢ It lies basal to tight junction.
➢ Microfilaments of two cells are connected by cadherins.
➢ Cytoplasmic face is linked to actin cytoskeleton.
➢ Actin myosin interaction can change the shape of the epithelium.
APPLIED PHYSIOLOGY
➢ Dysfunction of hemidesmosome also causes bullous pemphigoid.
The patients develop antibodies against integrins.
➢ Dysfunction of desmosome causes bullous pemphigoid
(autoimmune disease with tense blistering eruptions of the skin). The
patients with this disease develop antibodies against cadherins.
➢ Dysfunction of adherens junction and focal junction in colon due to
mutation of proteins results in colon cancer. It also leads to tumor
metastasis (spread of cancer cells from a primary tumor to other parts
of the body).
Junction Cytoskeletal Transmembrane Ties cell to
Anchor Linker

Desmosomes Intermediate Cadherin Cell

Filaments

Hemidesmosom Intermediate Integrins ECF

e Filaments

Adherens Actin Filaments Cadherin/Integrins Cell/ECF

Junction
CELL ADHESION MOLECULES (CAMS)
➢ Important cell surface proteins molecules that promotes cell–cell and
cell–matrix interactions.
➢ Important for many normal biological processes e.g. embryonic cell
migration, immune system functions, wound healing.
➢ Involved in intracellular signaling pathways (primarily for cell
death/survival, secretion etc.)
CAM 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.
➢ Interactions between CAMs can be mediated by

➢ Homophilic Binding: Binding of an adhesion molecule on one cell to the same

adhesion molecule on a second cell Cadherin – cadherin.
➢ Heterophilic Binding: An adhesion molecule on one cell type binds to a
different type of cell adhesion molecule on a second cell Selectins – mucins.
➢ Binding Through an Extracellular Linker Molecule: The linker molecule in
most cases is Laminin, a family of large cross shaped molecules with multiple
receptor domains.
4 Major Families of Cell Adhesion Molecules
● The cadherin superfamily
● The selectins
● The immunoglobulin superfamily
● The integrins
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.
● The Selectins
They act as receptors for carbohydrates (ligand or mucin) and are found
in platelets and endothelial cells.
● The Immunoglobulin Superfamily (IgG super family)
They form the cell adhesion molecules in nervous system.
● The Integrins
They form the focal adhesion and hemidesmosome.