Cellular Junctions – Types and Functions

What is Cellular Junctions or Cell junction?

• Cellular junctions, also known as cell junctions or junctional complexes, are critical components in the structure and function of eukaryotic organisms, particularly in animal cells. These structures consist of multiprotein complexes that facilitate crucial interactions within and between cells.
• The primary role of cellular junctions is to establish and maintain contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. This interaction is vital for the structural integrity and functional coordination of cellular communities. Furthermore, cellular junctions are instrumental in maintaining the paracellular barrier of epithelia and controlling paracellular transport, which is essential for the selective permeability of epithelial layers.
• There are various types of cellular junctions in animal cells, each serving distinct functions. These include tight junctions, gap junctions, and anchoring junctions. Tight junctions are imperative for creating a nearly impermeable barrier between cells, thereby controlling the movement of substances through the paracellular space. Gap junctions, also known as communicating junctions, enable direct communication between neighboring cells through the exchange of ions and small molecules. Anchoring junctions, including desmosomes and hemidesmosomes, provide mechanical stability by anchoring cells to each other or to the extracellular matrix.
• In plant cells, the equivalent of gap junctions is plasmodesmata, which are channels that traverse the cell walls of plant cells and allow for the transport of substances and signals between cells. Fungi have a similar structure known as septal pores, serving a comparable function in intercellular communication.
• Moreover, cell junctions play a crucial role in reducing stress placed upon cells, thereby contributing to the overall health and resilience of tissues. They are especially abundant in epithelial tissues, where they contribute to the tissue’s mechanical integrity and barrier functions.
• Therefore, cellular junctions are fundamental in both structuring the physical layout of tissues and enabling the dynamic interplay of communication and material exchange essential for the proper functioning of multicellular organisms. These structures exemplify the intricate and coordinated nature of cellular organization and highlight the complexity of biological systems.

Definition of Cellular Junctions or Cell junction

Cellular junctions, or cell junctions, are specialized structures in eukaryotic cells that facilitate adhesion and communication between adjacent cells or between a cell and the extracellular matrix. These junctions are essential for maintaining the structural integrity of tissues and enable coordinated cellular functions through material and signal exchange.

Types of Cellular Junctions

There are present different types of Cellular Junctions such as;

1. Tight Junctions (Zonula Occludens)

• Structure and Location Tight junctions, also known as occluding junctions or zonula occludens, are specialized structures in epithelial and endothelial cells. Located at the apex of the lateral plasma membranes, these junctions surround the cells, creating a selectively permeable seal. In thin sections, tight junctions appear as points where adjacent plasma membranes are fused, forming a network of ridges and complementary grooves. This structure, comprising two rows of proteins from adjacent cells, resembles a zipper, providing a leak-proof effect.
• Occurrence and Variations Tight junctions are found in both vertebrate and invertebrate animals, predominantly in epithelial tissues that interface with spaces or cavities. In invertebrates, similar structures are referred to as septate junctions, which differ in protein composition and arrangement.
• Functions
  • Barrier Formation: Tight junctions act as a permeability barrier, limiting the passage of molecules and ions between cells. This function is crucial in processes like nutrient diffusion from the intestinal lumen to the blood.
  • Cell Cohesion: They provide mechanical support to epithelial structures, ensuring cohesion.
  • Protein Movement Regulation: Tight junctions restrict the movement of integral membrane proteins, maintaining the specialized functions of different cell surfaces, such as exocytosis and receptor-mediated endocytosis.
• Molecular Composition
  • Transmembrane Proteins: Claudin and occludin are the primary transmembrane proteins in tight junctions. Claudins, varying in types, form homotypic complexes and are responsible for the selective permeability of ions and solutes. Occludin’s role, while less clear, is suggested to regulate macromolecular flux.
  • Cytoplasmic Adaptor Proteins: These proteins bind claudin and occludin to the actin cytoskeleton. They include a family of PDZ domain proteins (ZO-1, -2, -3), cingulin, and others. ZO proteins are vital for the organization of the tight junction and associated cytoskeleton.
• Functional Dynamics
  • Barrier and Proliferation Regulation: Tight junctions regulate both barrier functions and cell proliferation. This regulation involves interactions with transcription factors like ZONAB and YAP, influencing cellular processes like apoptosis and growth.
  • Interactions with Other Junctions: Tight junctions also interact with adherens junctions, linking them through proteins like ZO-1 and PATJ, contributing to epithelial cell polarity and tissue integrity.
• Physiological Impact
  • Paracellular Barrier: Tight junctions define the paracellular pathway, controlling the diffusion of ions and solutes between cells. Their selectivity depends on the type of claudins expressed and the physiological pH, influencing the permeability for cations and other solutes.
• Protein Roles in Tight Junctions
  • Scaffolding Proteins: Organize transmembrane proteins and link them to cytoplasmic proteins and actin filaments.
  • Signaling Proteins: Involved in junction assembly, barrier regulation, and gene transcription.
  • Regulation Proteins: Manage membrane vesicle targeting.
  • Transmembrane Proteins: Include junctional adhesion molecule, occludin, and claudin, with claudin being pivotal for selective permeability.

2. Anchoring Junctions

Anchoring junctions are specialized structures found in tissues where epithelial and endothelial cells come into contact. Located near the apical end of cells, adjacent to tight junctions, these junctions provide mechanical stability and maintain the structural integrity of tissues.

• Molecular Composition The primary components of anchoring junctions include cadherins and catenins, which are primary transmembrane adherence proteins, along with plaque proteins. These molecules work together to form the junctions and ensure cellular adhesion.
• Functions
  • Cellular Plasticity: Anchoring junctions contribute to maintaining the plasticity of cells, allowing them to maintain shape and coherence under stress.
  • Regulation of Passage: They regulate the movement of solutes, water, and lymphoid cells across connected cells, ensuring controlled material exchange and signaling.
• Types of Anchoring Junctions There are four main types of anchoring junctions:
  • Desmosomes: Link intermediate filaments of adjacent cells through cadherin proteins.
  • Hemidesmosomes: Attach intermediate filaments of a cell to the extracellular matrix via integrin proteins.
  • Adherens Junctions: Connect actin filaments of one cell to those of another or to the extracellular matrix, using cadherin, integrin, or nectins.
  • Focal Adherens: Specialized structures that anchor actin filaments to the extracellular matrix.
• Mechanical Cohesion and Stress Response Anchoring junctions are crucial in tissues exposed to mechanical stress, such as the skin and heart. They provide not only cellular cohesion but also enable the tissue to withstand and adapt to physical forces.
• Role in Tissue Architecture
  • Structural Cohesion: These junctions are integral to the overall structure of tissues, contributing to their mechanical properties and resilience.
  • Interactions with Cytoskeleton and Extracellular Matrix: The junctions facilitate connections between the cytoskeleton of one cell to that of another or to the extracellular matrix, reinforcing tissue structure and stability.

a. Desmosomes

• Desmosomes, also known as maculae adherentes, are specialized structures present in tissues subjected to severe mechanical stress, such as skin epithelia, bladder, cardiac muscles, and the neck of the uterus and vagina. They are categorized into three types: spot desmosomes, hemidesmosomes, and belt desmosomes.
• Spot Desmosomes (Macula Adherens)
  • Structure: Spot desmosomes are like rivets, approximately 0.5 µm in diameter, and provide mechanical stability by holding epithelial cells together. The plasma membranes of adjacent cells maintain a distance of 30-50 nm, with a central stratum rich in proteins and mucopolysaccharides.
  • Composition: They consist of a dense plaque of non-glycosylated proteins like desmoplakins I, II, and III, and keratin proteins (tonofilaments) that anchor at the plaque. Additionally, glycosylate proteins, desmogleins I and II, extend from the plaque into the plasma membrane as transmembrane linkers.
• Molecular Components of Desmosomes
  • Cadherins: Desmosomes contain transmembrane cadherins, including desmoglein (Dsg) and desmocollin (Dsc). These proteins form adhesive units through Ca2+-dependent hetero- and homo-dimers, and in certain conditions, Ca2+-independent heterodimers, providing strong intercellular adhesion.
  • Armadillo Proteins: Plakoglobin and plakophilin, members of the Armadillo protein family, interact with Dsg and Dsc. Plakoglobin facilitates desmosome assembly and can substitute for β-catenin in adherens junctions (AJ). It binds to desmoplakin, which in turn attaches to cytokeratin intermediate filaments. Plakophilin aids in the recruitment of Dsc2 and forms a scaffolding complex that regulates the strength of junctional integrity.
• Functional Dynamics of Desmosomes
  • Mechanical Stability: Desmosomes function as mechanical stabilizers in tissues by anchoring intermediate filaments composed of keratin or desmin to membrane-associated attachment proteins.
  • Cell-Cell Adhesion: Cadherin molecules extend through the cell membrane, binding to cadherins of adjacent cells, effectively creating strong intercellular adhesion points.
  • Junctional Integrity: The interaction between desmoplakin and intermediate filaments, regulated by complexes involving plakophilin and protein kinase C-α, is crucial for maintaining the structural integrity of the junctions.

b. Adherens junctions

Adherens junctions, also known as belt desmosomes or zonula adherens, are cellular structures found in the interface between columnar cells, typically located just below tight junctions.

• Structural Composition and Arrangement
  • Formation of Bands: These junctions form a band around the inner surface of the plasma membrane, functioning as a cellular girdle.
  • Microfilaments: The bands consist of 6-7 nm actin microfilaments and 10 nm intermediate microfilaments. The actin filaments are contractile, aiding in cell movement and shape, while the intermediate filaments provide structural support.
  • Membrane Proximity: The plasma membranes of adjacent cells in adherens junctions are parallel and thicker, with a separation of 15-20 nm. The space between these cells is filled with amorphous material.
• Functional Diversity and Cytoskeletal Connection
  • Anchoring to Actin Filaments: Adherens junctions anchor cells through their cytoplasmic actin filaments. This anchoring is vital for the mechanical integrity and flexibility of cellular tissues.
  • Morphological Variations: They exhibit considerable morphological diversity, including isolated streaks or spots and band-type arrangements encircling the cell. Spot-like adherens junctions, known as focal adhesions, help cells adhere to the extracellular matrix.
  • Contractile Function: The contractile nature of actin filaments in adherens junctions contributes to folding and bending of epithelial cell sheets, akin to a ‘drawstring’ effect.
• Role in Cell Adhesion and Cytoskeleton Regulation
  • Initiation of Cell–Cell Adhesion: Adherens junctions, predominantly comprising classical cadherins like E-cadherin, initiate and maintain cell–cell adhesion. These cadherins engage in Ca²⁺-dependent trans binding with cadherins on opposing cell surfaces.
  • Catenin Complexes: The cytoplasmic domain of E-cadherin forms complexes with β-catenin and α-catenin, which bind to F-actin and microtubules, integrating the adherens junctions with the cytoskeleton.
  • Mechanosensitivity and Strength: Mechanical force plays a crucial role in linking the E-cadherin-catenin complex to the actin cytoskeleton, enhancing cell adhesion. Vinculin, a mechanosensitive protein, contributes to this adhesion strength.
• Integration with Other Cellular Components
  • Nectin-Based Adhesions: Nectin, an immunoglobulin-like molecule, forms Ca²⁺-independent cell–cell adhesions at adherens junctions. It interacts with afadin and ZO-1, linking nectin-based complexes to the actin cytoskeleton.
  • Sequential Junction Formation: Nectin-based adhesions may precede and cooperate in the formation of adherens junctions, illustrating the sequential and cooperative nature of junctional protein activity in establishing mature cell–cell contacts.

c. Hemidesosomes

Hemidesmosomes are specialized cell structures resembling half desmosomes. They primarily function to connect the basal surface of epithelial cells to the underlying basal lamina.

• Structural Characteristics
  • Anchoring Role: Hemidesmosomes serve as anchoring sites for extracellular proteins like collagen, facilitating their attachment to the cell.
  • Comparison with Spot Desmosomes: While similar to spot desmosomes in function, hemidesmosomes differ in their location and structural components, connecting to the basal lamina rather than adjoining cells.
• Connection to Cytoskeleton and Extracellular Matrix
  • Link to Cytoskeleton: Hemidesmosomes create rivet-like links between the cytoskeleton of epithelial cells and extracellular matrix components, particularly the basal laminae.
  • Intermediate Filament Interaction: Like desmosomes, hemidesmosomes connect to intermediate filaments within the cytoplasm. However, they differ in their transmembrane components.
• Transmembrane Anchors
  • Integrins vs. Cadherins: Unlike desmosomes, which primarily utilize cadherins as transmembrane anchors, hemidesmosomes use integrins. This difference reflects their distinct roles and locations within the cell structure.

d. Focal adherens 

Focal adherens are specialized cellular structures that facilitate the connection between the cytoskeleton of a cell and its surrounding environment. They play a pivotal role in cell adhesion and signal transduction.

• Connection to the Cytoskeleton
  • Role of Actin Filaments: Focal adherens are directly connected to the cytoskeleton through actin filaments. This connection is crucial for maintaining the cell’s structural integrity and facilitating intracellular communication.
• Protein Composition
  • Integrins: In the intercellular membrane, focal adherens contain integrins, which are transmembrane proteins that play a key role in cell adhesion and signal transduction.
  • Plaque Proteins: Vinculin, a type of plaque protein, is present on the side of the focal adherens facing the plasma membrane. Vinculin plays a significant role in linking integrins to the actin cytoskeleton and is essential for the mechanical stability and signaling functions of focal adherens.
• Functions of Focal Adherens
  • Cell Adhesion and Mechanical Stability: Focal adherens are critical for cell adhesion, particularly in tissues subjected to mechanical stress. By linking the actin cytoskeleton to the extracellular matrix, they provide structural stability to the cells.
  • Signal Transduction: Through integrins, focal adherens participate in signal transduction processes, conveying signals from the extracellular environment to the cell’s interior. This function is essential for various cellular responses, including growth, differentiation, and migration.

3. Gap Junctions

Gap junctions, also known as nexuses, macula communicans, or communicating junctions, are specialized structures in higher animals that facilitate intercellular communication.

• Structural Features
  • Pore Formation: Each gap junction contains hollow round channels, known as pores. These are formed by two connexons (or hemichannels), each consisting of six protein subunits with four transmembrane domains.
  • Size and Variation: The diameter of these pores ranges from 1.5-2 nm, and the number of gap junctions varies among different cells.
• Mechanism of Action
  • Opening and Closing: The movement of the subunits within connexons leads to the opening and closing of the junctions. This mechanism is influenced by the level of Ca²⁺ ions, with permeability being inversely proportional to Ca²⁺ concentration.
  • Permeability and Ionic Connection: Gap junctions allow the transfer of small ions and molecules (up to 10,000 daltons), creating ionic or electronic connections between adjacent cells and facilitating changes in membrane potential.
• Distribution and Roles in Tissues
  • Presence in Cells: Gap junctions are found in embryonic cells and in adult tissues such as epithelia, cardiac, and liver cells.
  • Functions: These junctions permit the permeability of inorganic ions, sugars, amino acids, nucleotides, and various small molecules between adjacent cells. They are crucial for transferring action potentials in cardiac muscle cells, contributing to rhythmic heart contractions, and in electrical synapses in the brain.
• Chemical Communication and Connexon Interaction
  • Direct Cytoplasmic Communication: Gap junctions enable direct chemical communication between adjacent cellular cytoplasms through diffusion, bypassing extracellular fluid.
  • Connexon Structure: Composed of six connexin proteins, connexons form a cylinder with a central pore. Two adjacent cell connexons interact to form a complete gap junction channel, allowing efficient communication without leakage to the extracellular environment.
  • Specificity and Variation: Connexon pores vary in size and polarity, determined by the connexin proteins, thus can be specific to certain molecules or ions.
• Physiological Importance
  • Heart Muscle Coordination: Gap junctions are vital for the uniform contraction of heart muscle.
  • Brain Signaling: They play a significant role in signal transfer in the brain, with their absence linked to decreased cell density.
  • Cell Differentiation and Proliferation: In retinal and skin cells, gap junctions are essential for cell differentiation and proliferation.

4. Plasmodesmata

Plasmodesmata are fine cytoplasmic channels that facilitate intercellular communication in higher plants, connecting neighboring cells.

• Structural Characteristics
  • Cylindrical Shape and Size: Each plasmodesma is a nearly cylindrical, membrane-lined channel, typically 20-40 nm in diameter.
  • Central Structure – Desmotubule: At the center of a plasmodesma lies a narrow cylindrical structure known as the desmotubule. This structure is continuous with the membranes of the smooth endoplasmic reticulum (SER) in each connected cell.
  • Composition: The innermost layer of a plasmodesma is composed of the plasma membrane. Between the desmotubule and the plasma membrane is the annulus, a ring of cytosol.
  • Regulation of Molecule Movement: The annulus appears constricted, a feature that regulates the movement of molecules through it, effectively joining the cytosols of two adjacent cells.
• Functional Aspects of Plasmodesmata
  • Molecular Transfer: Plasmodesmata allow the passage of various molecules, including mRNA and large proteins, between cells. This transfer occurs through passive diffusion.
  • Nutrient Movement in Vascular Tissues: They play an essential role in the movement of nutrients within the vascular tissues of plants, facilitating efficient distribution of essential substances.

Examples of Cellular Junctions or Cell junction

FAQ

References

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