Cell Junctions: Types and Classifications

• Cell junctions facilitate connection between neighboring cells.
• They are also called intercellular junctions.
• Examples of intercellular junctions: tight junctions, gap junctions, adherens junctions, and desmosomes.
• Contact between the cell and extracellular matrix is called membrane junction.
• Examples of membrane junctions: focal adhesion and hemidesmosome.

Classifications of Junctions

• Junctions are classified into three types: occluding, communicating, and anchoring junctions.

Occluding Junctions

• These junctions prevent intercellular exchange of substances.
• Tight junctions belong to the category of junctions that prevent movement of ions and molecules from one cell to another.
• Occluding junctions are divided into tight junctions.

Tight Junctions

• Also called zonula occludens.
• They prevent passage of large molecules.
• Present in the apical margins of epithelial and endothelial cells in intestinal mucosa, wall of renal tubule, capillary wall, and choroid plexus.
• A tight junction is made up of a ridge which has two halves (from the two cells).
• The ridge is formed by tight junction strands made up of proteins.

Proteins of Tight Junctions

• Tight junction membrane proteins or integral membrane proteins: occludin, claudin, JAMs (junctional adhesion molecules).
• Scaffold proteins or peripheral membrane proteins or cytoplasmic proteins.
• Plaque proteins: cingulin, symplekin, and ZO-1,2,3.
• Based on its function, it is called an impermeable junction.

Functions of Tight Junctions

• Functions as a selective diffusion barrier between neighboring epithelial or endothelial cells; this is referred to as a barrier or gate function.
• Forms a selective barrier for small molecules and a total barrier for large molecules.
• Tight junctions in brain capillaries form the blood-brain barrier (BBB).
• Maintains the differential composition of proteins and lipids between the apical and basolateral plasma membrane domains.

Communicating Junctions

• Permit intercellular exchange of substances and are divided into gap junctions and chemical synapses.

Gap Junction

• Also called nexus.
• Allows passage of ions and small molecules between neighboring cells.
• It is present in the heart, basal part of epithelial cells of intestinal mucosa, etc.
• Each half of the channel is surrounded by six subunits of proteins called connexins or connexons.
• Diameter of the channel in gap junction is about 1.5 to 2.0 nm.
• The diameter of each channel is regulated by intracellular calcium ions; increased intracellular calcium ions decreases the diameter of the channel.

Chemical Synapse

• The junction between a nerve fiber and a muscle fiber, or between two nerve fibers, through which signals are transmitted by the release of chemical transmitters.

Applied Physiology

• Mutation to the genes encoding connexins causes diseases such as deafness, keratoderma, cataract, Charcot-Marie-Tooth disease, and Heterotaxia.

Anchoring Junctions

• They provide strength to the cells by acting like mechanical attachments.
• Responsible for the structural integrity of tissues and are present in heart muscles, epidermis of skin, etc.
• Anchoring junctions are divided into actin filament attachment and intermediate filament attachments.

Actin Filament Attachment

• Adherens junction
• Focal adhesion

Intermediate Filament Attachment

• Desmosome
• Hemidesmosome

Adherens Junction

• This is cell-to-cell junction, which connects the actin filaments of one cell to those of another cell.
• This junction forms a continuous adhesion (zonula adherens) just below the tight junctions.
• The membranes of the adjacent cells are held together by transmembrane proteins called cadherins.
• Adherens junctions are present in the intercalated discs between the branches of cardiac muscles.

Focal Adhesion

• This cell-to-matrix junctions, which connects the actin filaments of the cell to the extracellular matrix.
• The transmembrane protein that holds the cell membrane and the matrix are called integrins.

Desmosome

• This is a cell-to-cell junction where intermediate filaments connect two adjacent cells.
• It is also called macula adherens.
• They function like tight junctions.
• Proteins involved in desmosomes are mainly cadherins.

Hemidesmosome

• This is a cell-to-matrix junction, which connects the intermediate filaments of the cell to the extracellular matrix.
• It is also called half-desmosome.
• The proteins involved here are integrins.

Applied Physiology

• Dysfunction of adherens junction and focal junction in the colon due to mutation of protein results in colon cancer.
• It also leads to tumor metastasis.
• Dysfunction of desmosome causes bullous pemphigoid (autoimmune disease).
• Dysfunction of hemidesmosome also causes bullous pemphigoid.

Cell Adhesion Molecules (CAMs)

• CAMs are protein molecules responsible for the attachment of cells to their neighbor or to basal lamina.
• These molecules form the important structures of intercellular connections and are responsible for structural organization of tissues.

Types of Cell Adhesion Molecules

• Cadherins, which form the molecular limbs between neighboring cells.
• Integrins, which form the focal adhesions and hemidesmosomes.
• Immunoglobulin (Ig) superfamily, which forms the cell adhesion molecules.
• Selectins, which act as receptors for carbohydrate ligands and are found in platelets and endothelial cells.