How Small Solutes Traverse Cell Junctions

Gap junctions are intercellular channels that allow the passage of small molecules and ions directly from the cytoplasm of one cell to another. These junctions are formed by the assembly of membrane proteins called connexins, which create a pore with a diameter of 1.5-2 nm. Gap junctions are found in many animal tissues and are particularly important in the muscle tissue of animals' hearts, allowing ions to pass rapidly from cell to cell and coordinating cardiac muscle contraction.

Gap junctions are channels that allow the passage of small molecules, ions, and electrical signals between cells

Gap junctions are clusters of intercellular channels that allow the passage of small molecules, ions, and electrical signals between cells. They are found in virtually all cells in solid tissues.

Gap junctions are formed by connexons, which are themselves made up of six connexin proteins. Connexons from adjacent cells join to form a complete gap junction channel. This allows the passage of small molecules, ions, and electrical signals between cells.

The connexins that make up connexons can vary, and different connexins have different properties. For example, some connexins may be more permeable to certain molecules than others. This diversity in connexins allows for a wide range of functions in tissue and organ biology.

The passage of molecules through gap junctions is not absolute, and the permeability of gap junctions can be regulated. For example, the permeability of gap junctions can be reduced by decreasing the cytosolic pH or increasing the cytosolic concentration of free Ca2+.

Tight junctions form an impermeable barrier between cells, preventing the leakage of molecules and maintaining cell polarity

Tight junctions, also known as zonula occludens, form an almost completely impermeable barrier between cells, preventing the leakage of molecules and maintaining cell polarity. They are found in the epithelia, which are the coverings of the body's internal and external surfaces, including organs, blood vessels, and cavities.

Tight junctions are composed of a network of sealing strands, with each strand acting as an independent barrier to the flow of ions. The strands are made up of transmembrane proteins called claudins, which are embedded in the plasma membranes of adjacent cells. The extracellular domains of these proteins join directly to one another, occluding the intercellular space. The claudins are considered the backbone of the tight junction strands.

Tight junctions perform two vital functions. Firstly, they limit the passage of molecules and ions through the space between cells, forcing most materials to enter the cells through diffusion or active transport. Secondly, they block the movement of integral membrane proteins between the apical and basolateral domains of the plasma membrane in each epithelial cell. This allows the apical and basolateral surfaces of the cell to maintain their special functions, such as receptor-mediated endocytosis at the apical surface and exocytosis at the basolateral surface.

Tight junctions also support the maintenance of cell polarity by restricting the intermixing of apical and basolateral transmembrane components. They form the border between the apical and basolateral cell surface domains in polarised epithelia.

Desmosomes are rivets that hold cells together, preventing them from shearing apart

Desmosomes are composed of desmosome-intermediate filament complexes (DIFCs), a network of cadherin proteins, linker proteins, and intermediate filaments. The DIFCs can be divided into three regions: the extracellular core region ("desmoglea"), the outer dense plaque (ODP), and the inner dense plaque (IDP).

The extracellular core region, approximately 34 nm in length, contains desmoglein and desmocollin, which are in the cadherin family of cell adhesion proteins. Both have five extracellular domains and calcium-binding motifs. Extracellular calcium helps form the cadherin adhesion by allowing the cadherin extracellular domain on desmoglein and desmocollin to become rigid. They bind to each other via heterophilic interactions in the extracellular space near their N-termini, in contrast with the homophilic binding characteristic of other cadherins.

The outer dense plaque, which is about 15–20 nm in length, contains the intracellular ends of desmocollin and desmoglein, the N-terminus side of desmoplakin, and the armadillo family of mediatory proteins plakoglobin and plakophilin. Armadillo proteins are involved in mediating attachment to intracellular filaments and cell membrane proteins.

The inner dense plaque, also about 15–20 nm in length, contains the C-terminus end of desmoplakin and their attachment to keratin intermediate filaments. Desmoplakin is the most abundant part of the desmosome, as it operates as the mediator between the cadherin proteins in the plasma membrane and the keratin filaments.

Desmosomes play a crucial role in tissue integrity and are essential for maintaining strong cell-to-cell adhesion in stratifying epithelia. They are also important in tissue differentiation and development. Mutations in desmosomal genes can lead to various diseases, including arrhythmogenic cardiomyopathy, epidermal autoimmune disorders such as pemphigus, and blistering diseases such as pemphigus vulgaris and pemphigus foliaceus.

Adherens junctions are formed by cadherins and provide strong mechanical attachments between cells

Adherens junctions are composed of the following proteins:

• Cadherins
• P120 (sometimes called delta catenin) binds the juxtamembrane region of the cadherin
• Γ-catenin or gamma-catenin (plakoglobin) binds the catenin-binding region of the cadherin
• Α-catenin or alpha-catenin binds the cadherin indirectly via β-catenin or plakoglobin and links the actin cytoskeleton with cadherin

Adherens junctions are particularly important in epithelial and endothelial tissues, where they are usually more basal than tight junctions. They can also be found in non-epithelial, non-endothelial cells, such as cardiomyocytes, in the form of fascia adherens.

Hemidesmosomes are similar to desmosomes but attach epithelial cells to the basal lamina

Hemidesmosomes are multiprotein complexes that facilitate the stable adhesion of basal epithelial cells to the underlying basement membrane. They are similar in form to desmosomes when visualised by electron microscopy. However, desmosomes attach to adjacent cells, whereas hemidesmosomes attach epithelial cells to the basal lamina.

Hemidesmosomes are highly specialised integrin-mediated epithelial attachment structures. They make cells firmly adhere to the extracellular matrix by establishing a link between the underlying basement membrane and the internal mechanical stress-resilient keratin intermediate filament network.

Hemidesmosomes can be categorised into two types based on their protein constituents. Type 1 hemidesmosomes are found in stratified and pseudo-stratified epithelium, and have five main elements: integrin α6β4, plectin in its isoform 1a, tetraspanin protein CD151, BPAG1e, or bullous pemphigoid antigen isoform e, and BPAG2. Type 2 hemidesmosomes are found in simple epithelia, such as that of the intestine, and contain integrin α6β4 and plectin without the BP antigens.

Hemidesmosomes are involved in signalling pathways, such as keratinocyte migration or carcinoma cell intrusion. They are also linked to keratin by plectin isoform 1a from the plakin protein family.

Keeping the basal epidermal keratinocytes attached to the basal lamina is vital for skin homeostasis. Genetic or acquired diseases that cause disruption of hemidesmosome components can lead to skin blistering disorders between different layers of the skin. These are collectively known as epidermolysis bullosa.

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