Download Adherens Junctions

JUNCTION BETWEEN CELLS
In many animal tissues (e.g., connective tissue), each cell is separated from the next by an
extracellular coating or matrix.
However, in some tissues (e.g., epithelia), the plasma membranes of adjacent cells are pressed
together. Four kinds of junctions occur in vertebrates:
Tight junctions
Adherens junctions
Gap junctions
Desmosomes
In many plant tissues, it turns out that the plasma membrane of each cell is continuous with that of
the adjacent cells. The membranes contact each other through openings in the cell wall called
Plasmodesmata.
Tight Junctions
Epithelia are sheets of cells that provide the interface between masses of cells and a cavity or space
(a lumen).
The portion of the cell exposed to the lumen is called its apical surface.
The rest of the cell (i.e., its sides and base) make up the basolateral surface.
Tight junctions seal adjacent epithelial cells in a narrow band just beneath their apical surface.
Tight junctions perform two vital functions:
They prevent the passage of molecules and ions through the space between cells. So materials must
actually enter the cells (by diffusion or active transport) in order to pass through the tissue. This
pathway provides control over what substances are allowed through.
They block the movement of integral membrane proteins (red and green ovals) between the apical
and basolateral surfaces of the cell. Thus the special functions of each surface, for example
receptor-mediated endocytosis at the apical surface
exocytosis at the basolateral surface
can be preserved.
The Epithelia of the Human Lung: an example
The epithelial cells of the human lung express
a growth stimulant, called heregulin, on their apical surface and
its receptors on the basolateral surface. (These receptors also respond to epidermal growth factor
(EGF), and mutant versions have been implicated in cancer. [Link])
As long as the sheet of cells is intact, there is no stimulation of its receptors by heregulin thanks to
the seal provided by tight junctions.
However, if the sheet of cells becomes broken, heregulin can reach its receptors. The result is an
autocrine stimulation of mitosis leading to healing of the wound.
Several disorders of the lung
the chronic bronchitis of cigarette smokers
asthma
cystic fibrosis
increase the permeability of the airway epithelium. The resulting opportunity for autocrine
stimulation may account for the proliferation (piling up) of the epithelial cells characteristic of these
disorders. Link to pictures showing the proliferation of epithelial cells ("Squamous epithelium") in
cigarette smokers.
Adherens Junctions
Adherens junctions provide strong mechanical attachments between adjacent cells.
They hold cardiac muscle cells tightly together as the heart expands and contracts.
They hold epithelial cells together.
They seem to be responsible for contact inhibition.
Some adherens junctions are present in narrow bands connecting adjacent cells.
Others are present in discrete patches holding the cells together.
Adherens junctions are built from:
cadherins — transmembrane proteins (shown in red) whose
extracellular segments bind to each other and
whose intracellular segments bind to
catenins (yellow). Catenins are connected to actin filaments
Inherited mutations in a gene encoding a cadherin can cause stomach cancer. Mutations in a gene
(APC), whose protein normally interacts with catenins, are a common cause of colon cancer.
Loss of functioning adherens junctions may accelerate
the edema associated with sepsis;
tumor metastasis.
Gap Junctions
Gap junctions are intercellular channels some 1.5–2 nm in diameter. These permit the free passage
between the cells of ions and small molecules (up to a molecular weight of about 1000 daltons).
They are cylinders constructed from 6 copies of transmembrane proteins called connexins.
Because ions can flow through them, gap junctions permit changes in membrane potential to pass
from cell to cell.
Examples:
The action potential in heart (cardiac) muscle flows from cell to cell through the heart providing the
rhythmic contraction of the heartbeat.
At some so-called electrical synapses in the brain, gap junctions permit the arrival of an action
potential at the synaptic terminals to be transmitted across to the postsynaptic cell without the
delay needed for release of a neurotransmitter.
As the time of birth approaches, gap junctions between the smooth muscle cells of the uterus
enable coordinated, powerful contractions to begin.
Several inherited disorders of humans such as
certain congenital heart defects and
certain cases of congenital deafness
have been found to be caused by mutant genes encoding connexins.
Desmosomes
Desmosomes are localized patches that hold two cells tightly together. They are common in epithelia
(e.g., the skin). Desmosomes are attached to intermediate filaments of keratin in the cytoplasm.
Pemphigus is an autoimmune disease in which the patient has developed antibodies against proteins
(cadherins) in desmosomes. The loosening of the adhesion between adjacent epithelial cells causes
blistering.
Carcinomas are cancers of epithelia. However, the cells of carcinomas no longer have desmosomes.
This may partially account for their ability to metastasize.
Hemidesmosomes
These are similar to desmosomes but attach epithelial cells to the basal lamina ("basement
membrane" – View) instead of to each other.
Pemphigoid is an autoimmune disease in which the patient develops antibodies against proteins
(integrins) in hemidesmosomes. This, too, causes severe blistering of epithelia.
Plasmodesmata
Although each plant cell is encased in a boxlike cell wall, it turns out that communication between
cells is just as easy, if not easier, than between animal cells. Fine strands of cytoplasm, called
plasmodesmata, extend through pores in the cell wall connecting the cytoplasm of each cell with
that of its neighbors.
Plasmodesmata provide an easy route for the movement of ions, small molecules like sugars and
amino acids, and even macromolecules like RNA and proteins, between cells. The larger molecules
pass through with the aid of actin filaments.
Plasmodesmata are sheathed by a plasma membrane that is simply an extension of the plasma
membrane of the adjoining cells. This raises the intriguing question of whether a plant tissue is really
made up of separate cells or is, instead, a syncytium: a single, multinucleated cell distributed
throughout hundreds of tiny compartments``
pemphigus
Pemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but
which are often painful
Pathophysiology
It is an autoimmune disease caused by antibodies directed against both desmoglein 1 and
desmoglein 3 resulting in the loss of cohesion between keratinocytes in the epidermis, classified as a
type II hypersensitivity reaction. It is characterized by extensive flaccid blisters and mucocutaneous
erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly
proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and
erythematoses) are more desmoglein 1 heavy. It arises most often in middle-aged or older people,
usually starting with a blister that ruptures easily. The lesions can become quite extensive. The
pathogenesis of the disease involves autoantibodies against desmosome proteins, separating
keratinocytes from the basal layer of the epidermis. On histology, the basal keratinocytes are usually
still attached to the basement membrane leading to the appearance and thus the term,
"tombstoning".
Transudative fluid accumulates in between the keratinocytes and basement membrane (suprabasal
split), forming a blister and resulting in what is known as a positive Nikolsky's sign. This is a
contrasting feature from bullous pemphigoid, where the detachment occurs between the epidermis
and dermis (subepidermal bullae).
Diagnosis
On a physical exam, pemphigus vulgaris has flat bullae and a positive Nikolsky's sign. The gold
standard for diagnosis is a punch biopsy of the lesion with direct immunofluorescent staining,
showing acantholytic cells. These can also be seen on a Tzanck smear. These cells are basically
rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion
protein: Desmoglein.
Pemphigus vulgaris is easy to confuse with impetigo and candidiasis. IgG4 is considered pathogenic.
The diagnosis can be confirmed by testing for the infections that cause these other conditions, and
by a lack of response to antibiotic treatment. [2] Eosinophils tend to be found within the blisters and
provide an important clue supporting bullous pemphigoid as the diagnosis.
Treatment
Corticosteroids and other immunosuppressive drugs are the mainstay of treatment. Based on recent
studies, corticosteroids can be used in Pulse Therapy/Supra-pharmacological doses once a month to
decrease Hypothalamo-pituitary axis inhibition. IVIg, rituximab, mycophenolate mofetil,
methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of
success. It is a difficult disease to control