Intercellular junctions
2 broad groups:
• Junctions that fasten the cells to one another and to the surrounding tissues
• Junctions that permit transfer of ions and other molecules from one cell to
another
Intercellular junctions in the mucosa of the
small intestine
Tight junctions (Zonula occludens)
• Surround the apical margin of the epithelia in the intestinal mucosa, renal tubules, choroid plexus
• Important for endothelial barrier function and endothelium-dependant vasodilatation
• Made up of ridges, half from each cell, which adhere strongly at the cell junctions and obliterate
the space between the cells
• Transmembrane membrane proteins: Occludin, Junctional adhesion molecules and Claudin
• Permit the passage of ions, solute and intracellular signalling molecules (paracellular pathway)
• Degree of leakiness varies, depending on proteins present
Zonula adherens
• Continuous structure on the basal side of the zonula occludens
• Major site for the attachment of intracellular microfilaments
Desmosomes
• Apposed thickenings of the membranes of two adjacent cells
• Intermediate filaments are attached to the thickened area
• Intercellular space between the membrane thickenings contains filamentous material (Cadherins)
Hemidesmosomes
• Attach the cells to the underlying basal lamina
• Connected intracellularly to Intermediate filaments
• Contains Integrins
• FOCAL ADHESIONS also attach cells to their basal laminas
• They are labile structures associated with Actin filaments
• Play an important role in cell movement
Gap junctions
Gap junctions
• Intercellular space is 4nm at gap junctions
• Units called Connexons in the cell membrane of each cell are lined up with one another to form the
dodecameric gap junction (12 subunits)
• Each Connexon is made up of 6 subunits called Connexins
• Permits substances to pass between the cells without entering the ECF
• Pore diameter is 0.8 to 1.4 nm
• Permits passage of ions, sugars, amino acids and other solutes with molecular weights up to 1000 Da
Gap junctions
• Permit rapid propagation of electrical activity from cell to cell as well as exchange of chemical
messengers and intracellular signalling molecules
• Particular connexin subunits that make up connexons determine their permeability and selectivity
• Connexons can also provide a passage (Connexin semichannels) for regulated passage of small
molecules between the cytoplasm and the ECF
• Allows additional signalling pathways between and among the cells in a tissue
Connexins in disease
• 20 different genes code for connexins in humans
• Mutations in these genes lead to diseases that are highly selective in terms of the tissues involved
and the type of communication between the cells produced
• About 20 different human diseases have been identified till date
• Skin disorders (Clouston syndrome and erythrokeratoderma variabilis)
• Inherited deafness
• Predisposition to myoclonic epilepsy
• Predisposition to arteriosclerosis
• Cataract
• Idiopathic atrial fibrillation
• X-linked Charcot-Marie-Tooth disease
Cytoskeleton
Microtubules
• Long, hollow structures with 5nm walls surrounding a cavity 15nm in diameter
• Made up of α and β tubulin subunits
• Gamma tubulin is associated with the production of microtubules by the centrosomes
• Αlpha and beta subunits form heterodimers, which aggregate to form long tubes made up of
stacked rings. Each ring contains 13 subunits.
• Tubules interact with GTP to facilitate their formation
• Polar structures, with assembly predominating at the “plus” end and disassembly predominating
at the “minus” end
Microtubules
• Both processes occur simultaneously in vitro
• Growth of microtubules is temperature sensitive; disassembly is favoured under cold condition
• Variety of cellular factors can directly interact with the microtubules in the cell
• Dynamic portion of the cytoskeleton
• Provide tracks for molecular motors to move transport vesicles, organelles such as secretory granules and
mitochondria
• Also form the spindle
• Cargo can be transported in either direction along the microtubules
Applied aspects
• Several drugs disrupt cellular function through interaction with microtubules
• Colcichine and Vinblastine prevent microtubule assembly
• Paclitaxel (Taxol) binds to microtubules and makes them so stable that the organelles cannot
move; mitotic spindles cannot form and the cells die
Intermediate filaments
• 8 to 14nm in diameter; made up of various subunits
• Some connect the nuclear membrane to the cell membrane
• Form a flexible scaffolding for the cell and help it to resist external pressure
• Absence of intermediate filaments causes the cells to rupture more easily
• Blistering of skin is common in abnormalities of intermediate filaments in humans
• Constituent proteins are cell-specific and used as cellular markers
• Vimentin – Fibroblasts; Cytokeratin – epithelial cells
Microfilaments
• Long, solid fibres; 5-9nm in diameter; made up of Actin
• F-actin fibres attach to various parts of the cytoskeleton; found in microvilli and lamellipodia
• Actin fibres interact with integrin receptors and form Focal adhesion complexes; serve as points of
traction with the surface over which the cell pulls itself
• Some molecular motors use microfilaments as tracks
