Cell Adhesions, Junctions, and Extracellular Structures

Detailed Briefing: Cell Adhesions, Cell Junctions, and Extracellular Structures

Introduction

Multicellular organisms depend on the intricate organization of cells into tissues, which then form complex structures like organs. This organization is made possible by various forms of cell-cell and cell-extracellular matrix (ECM) attachments. This briefing document synthesizes information from the provided sources to detail these structures in both animal and plant cells, their molecular components, and their vital functions in maintaining tissue integrity, facilitating communication, and regulating cellular processes.

I. Cell-Cell Junctions in Animals

Animal cells employ specialized structures called cell-cell junctions to form long-term associations within tissues and organs. There are three main types: Adhesive junctions, Tight junctions, and Gap junctions.

A. Adhesive Junctions

Adhesive junctions link cells together, anchoring the cytoskeleton to the cell surface and enabling cells to function as a unit, particularly in resisting mechanical stress. They are dynamic structures, capable of assembly and disassembly in response to cellular events, and are involved in cell signaling, movement, proliferation, and survival.

1. Key Components:

◦ Adhesion Proteins: Primarily transmembrane proteins whose extracellular portions interact with similar proteins on neighboring cells. Homophilic interactions: Cells with identical receptors interact. Heterophilic interactions: Cells with different receptors interact.

◦ Linker Proteins: Connect transmembrane adhesion proteins to the cytoskeleton.

◦ Cadherins: A family of transmembrane proteins crucial for cell-cell adhesion, characterized by "repeats" in their extracellular domain, a transmembrane domain, and varying cytosolic ends. Their binding is calcium-dependent. Different cadherin types are expressed in specific tissues (e.g., E-cadherin in epithelial cells, P-cadherin in placenta). The quantity and type of cadherins help segregate cells into specific tissues, as demonstrated by "L cells" experiments where E-cadherin-expressing cells segregate from P-cadherin-expressing cells. Epithelial-Mesenchymal Transition (EMT): A process involving changes in cadherin expression, leading to the breakdown of epithelium into migratory mesenchymal cells. This is relevant in embryonic development and cancer metastasis, where cancer cells often reduce E-cadherin expression.

2. Types of Adhesive Junctions:

◦ Adherens Junctions: Cadherin-mediated junctions that interact with actin microfilaments. "They form a continuous belt that encircles the cell near the apical end of the lateral membrane." Associated Proteins: β-catenin: Binds to the cytosolic tail of cadherin, also functions in the Wnt pathway. α-catenin: Binds β-catenin and recruits F-actin to the junction. When stretched, it exposes binding sites for vinculin, strengthening the actin connection. p120 catenin (p120ctn): Binds to the cytoplasmic tail of cadherins, regulating their stability and endocytosis.

◦ Desmosomes: "Button-like points of strong adhesion between adjacent cells in a tissue." Provide structural integrity and are abundant in mechanically stressed tissues like skin, heart muscle, and uterus. Cadherins: Desmocollins and Desmogleins. Associated Proteins: Plakoglobin: Binds desmocollin. Desmoplakin: Binds plakoglobin and attaches to intermediate filaments (e.g., vimentin, desmin, keratin). Plakophilin: Binds cadherins and desmoplakin, potentially stabilizing desmosomes. Form a "thick plaque" beneath the plasma membrane. * Defects in desmosomal components can lead to severe conditions like blistering diseases of the skin (e.g., pemphigus), as highlighted in "Human Connections: The Costly Effects of Weak Adhesion."

3. Other Molecules in Transient Cell-Cell Adhesions:

◦ Lectins: Carbohydrate-binding proteins that promote cell-cell adhesion by binding specific sugars on cell surfaces, linking cells together.

◦ Cell Adhesion Molecules (CAMs): Members of the immunoglobulin superfamily (IgSF). N-CAM (neural cell adhesion molecule): Involved in outgrowth and bundling of axons. Exhibit homophilic interactions via well-organized loops similar to immunoglobulins.

◦ Selectins: Mediate transient interactions, particularly in leukocyte adhesion to endothelial cells during inflammation. L-selectin (leukocytes), E-selectin (endothelial cells), P-selectin (platelets and endothelial cells). "Initial attachment of leukocytes is mediated by binding of selectins on the leukocyte to carbohydrates on the surface of the endothelial cells and vice versa."* Stable adhesions involve integrins and ICAMs.

B. Tight Junctions (TJs)

Tight junctions create impermeable seals between epithelial cells, forming a barrier that regulates the movement of molecules and ions across cell layers.

• Function: "They form a continuous belt around the apical ends of lateral surfaces of each cell; molecules cross the cell layer by passing through the cells."

• Structure:

◦ "Membranes joined along ridges."

◦ Consist of "a continuous row of tightly packed transmembrane proteins" forming an interconnected network of ridges.

◦ Major Transmembrane Proteins: Occludin. Junctional Adhesion Molecules (JAMs)(IgSF proteins). * Claudins: Proteins with four membrane-spanning domains. Claudins in adjacent cells interlock to form a tight seal and can form "ion-selective pores to allow passage of specific ions," a process called paracellular transport. Different claudins confer different permeability properties.

• Other Roles: TJs also act as "fences" to block the lateral movement of lipids (in the outer monolayer) and integral membrane proteins within the plasma membrane, maintaining distinct functional domains.

C. Gap Junctions

Gap junctions provide direct electrical and chemical communication between adjacent cells by forming open channels.

• Structure:

◦ "A gap junction is a region where the plasma membranes of cells are aligned and brought into contact, with a very small gap between."

◦ Connexons: Hollow cylindrical assemblies of six connexin protein subunits (in vertebrates) that span the plasma membrane. Connexons from adjacent cells align to form a channel about 3 nm wide.

◦ Innexins: Invertebrate equivalent of connexins.

• Function:

◦ Allow the passage of ions and small molecules (up to ~1200 Da), such as sugars, amino acids, and nucleotides, directly from one cell to another.

◦ "Allow adjacent cells to be in direct electrical and chemical communication with each other."

◦ Crucial for rapid communication in tissues like muscle and nerve (e.g., heart muscle beating).

◦ Their permeability can be influenced by electrical potential and second messenger concentrations.

◦ Defects are linked to various human disorders (e.g., neurodegenerative diseases, skin disorders, cataracts, deafness).

II. The Extracellular Matrix (ECM) of Animal Cells

The ECM is a crucial non-cellular component of tissues, providing structural support, facilitating cellular processes (division, motility, differentiation, adhesion), and defining tissue shape and mechanical properties. It takes on various forms (e.g., rigid in bone, flexible in cartilage, gelatinous in connective tissue). Epithelial cells produce a specialized ECM called the basal lamina, part of the basement membrane.

A. Three Classes of ECM Molecules

1. Structural Proteins: Provide strength and flexibility.

◦ Collagens: The most abundant ECM component in animals, forming fibers with high tensile strength. "Account for as much as 25–30% of total body protein." Secreted by fibroblasts and other connective tissue cells. Structure: Rigid triple helix of three intertwined polypeptide α chains. High in glycine, hydroxylysine, and hydroxyproline. Assembly: Three α chains form procollagen in the ER lumen, which is then secreted and cleaved by procollagen peptidase to form collagen molecules. These spontaneously associate into fibrils and then fibers. Stability reinforced by hydrogen bonds (involving hydroxylysine and hydroxyproline) forming crosslinks. * Various types (at least 15), tissue-specific. Defects can cause diseases like Ehlers-Danlos syndrome. Vitamin C is essential for collagen synthesis.

◦ Elastins: Provide elasticity and flexibility to the ECM (e.g., in lungs, arteries, skin). Rich in glycine and proline. Crosslinked by covalent bonds between lysine residues, allowing stretching and recoiling. Aging can lead to increasing crosslinking and loss of elasticity in collagens and elastins.

2. Protein-Polysaccharide Complexes: Provide the hydrated matrix.

◦ Proteoglycans: Glycoproteins with numerous glycosaminoglycans (GAGs) attached to a core protein. GAGs: Large carbohydrates with repeating disaccharide units (e.g., chondroitin sulfate, keratan sulfate, hyaluronate). Hydrophilic, with many negatively charged sulfate and carboxyl groups, attracting water and cations to form a gelatinous matrix. Most GAGs are covalently bound to proteins to form proteoglycans. Vary greatly in size. * Hyaluronate: An exception, occurring as a free molecule or as a backbone for proteoglycan complexes in cartilage. Has lubricating properties (e.g., in joints).

3. Adhesive Glycoproteins: Allow cells to attach to the matrix.

◦ Fibronectins: A family of closely related adhesive glycoproteins found in soluble form (plasma fibronectin), insoluble fibrils in ECM, and associated with cell surfaces. Consist of two large subunits linked by disulfide bonds, with rod-like domains. Have multiple binding sites for ECM macromolecules (collagen, heparin, fibrin) and cell surface receptors. Recognize and bind cell surface receptors via the RGD (arginine-glycine-aspartate) sequence. Crucial for cell migration, acting as a "bridging molecule that attaches cells to the ECM." Involved in blood clotting (plasma fibronectin binds fibrin and platelets).

◦ Laminins: Major adhesive glycoproteins in basal laminae. Underlie epithelial cells, separating them from connective tissues. Also surround muscle, fat, and Schwann cells. Consist of three long polypeptides (α, β, γ) held together by disulfide bonds in a cross shape. Have binding sites for type IV collagen, heparin, heparan sulfate, nidogen, and cell surface receptors. Nidogen reinforces binding between type IV collagen and laminin networks. The basal lamina acts as a structural support and a permeability barrier (e.g., kidney filter). * Matrix metalloproteinases (MMPs): Enzymes that degrade ECM locally, allowing cell passage (important for leukocyte invasion, and cancer cell invasiveness).

B. Integrins: Cell Surface Receptors for ECM

Integrins are a large family of transmembrane proteins that "integrate the cytoskeleton with the extracellular matrix."

• Structure: Consist of two large transmembrane polypeptides, α and β subunits, which noncovalently associate.

• Binding Specificity: Extracellular parts form binding sites for ECM proteins (fibronectins, laminins), with specificity largely dependent on the α subunit. Many recognize the RGD sequence.

• Interaction with Cytoskeleton: Integrin tails interact with cytosolic linker proteins, connecting integrins to the cytoskeleton.

◦ Focal Adhesions: Found in migratory and non-epithelial cells (e.g., fibroblasts). Contain clustered integrins that interact with actin microfilaments via linker proteins (talin, vinculin, α-actinin). Important for cell movement and attachment.

◦ Hemidesmosomes: Found in epithelial cells. Contain α6β4 integrin, which attaches to intermediate filaments (typically keratin) via a dense plaque of linker proteins (e.g., plectin, BPAG2, BPAG1). Crucial for skin mechanical strength; defects cause blistering diseases like bullous pemphigoid and epidermolysis bullosa simplex (EBS).

• Signaling: Integrins participate in bidirectional signaling ("inside-out" and "outside-in" signaling).

◦ Anchorage-dependent growth: Most normal cells require attachment to a substratum (ECM) to grow; cancer cells often lose this dependency.

◦ Kinases (FAK, Kindlins, ILK) are recruited to focal adhesions, influencing cellular processes.

• Dystrophin/Dystroglycan Complex: A third type of ECM attachment in striated muscle cells, forming costameres.

◦ Dystrophin: A huge cytosolic protein that interacts with actin.

◦ Dystroglycan complex: Integral membrane protein linked to dystrophin, which binds to laminin in the ECM.

◦ Mutations in the dystrophin gene cause muscular dystrophies (Duchenne and Becker muscular dystrophy), leading to muscle degeneration due to increased susceptibility to damage.

III. The Plant Cell Surface

Plant cells, unlike animal cells, are surrounded by rigid cell walls, which provide structural framework, protect from damage and pathogens, and serve as a permeability barrier.

A. Plant Cell Wall Composition

The plant cell wall is a network of long fibers embedded in a matrix of branched molecules.

• Cellulose Microfibrils:

◦ Predominant polysaccharide, "the single most abundant organic macromolecule on Earth."

◦ Long, ribbon-like structures of β-D-glucose units stabilized by intramolecular hydrogen bonds.

◦ 50-60 cellulose molecules associate to form microfibrils; microfibrils twist into larger macrofibrils (as strong as steel).

◦ Synthesized by rosettes (cellulose-synthesizing enzyme complexes) in the plasma membrane.

• Hemicelluloses: Heterogeneous polysaccharides with a long linear chain of a single sugar and short side chains, forming a rigid network.

• Pectins: Branched polysaccharides that form the gel-like matrix in which cellulose microfibrils are embedded. They also bind adjacent cell walls together and trap water.

• Extensins: Rigid, rod-like glycoproteins tightly woven into the polysaccharide network, becoming covalently crosslinked to one another and to cellulose, providing mechanical support.

• Lignins: Very insoluble polymers of aromatic alcohols, found mainly in woody tissues. Localized between cellulose fibrils, they "function to resist compression forces," making wood strong and rigid.

B. Cell Wall Synthesis Stages

The cell wall is secreted in layers:

1. Middle Lamella: The first structure, shared by neighboring cell walls, holding adjacent cells together.

2. Primary Cell Wall:

◦ Formed while cells are still growing (thin, flexible).

◦ A loosely organized network of cellulose, hemicellulose, pectins, and glycoproteins.

◦ Cellulose microfibril formation by rosettes is influenced by microtubules.

◦ Expansins: Proteins that help cell walls retain pliability, potentially by disrupting hydrogen bonding in glycans, allowing for microfibril rearrangement. Activity may be stimulated by the plant hormone auxin.

3. Secondary Cell Wall:

◦ Added after cell growth has ceased (thicker, more rigid).

◦ Composed mainly of densely packed cellulose microfibrils arranged in parallel and at angles to adjacent layers, along with lignins. This organization confers great strength and rigidity.

C. Plasmodesmata

Plasmodesmata are cytoplasmic channels through openings in the cell wall, allowing cytoplasmic continuity and direct communication between adjacent plant cells.

• Structure:

◦ Lined with plasma membrane common to the two cells.

◦ Desmotubule: A single tubular structure, derived from and continuous with the endoplasmic reticulum (ER) of both cells, typically lies in the central channel.

◦ Annulus: The ring of cytosol between the desmotubule and the membrane lining the plasmodesma, providing cytoplasmic continuity.

• Function:

◦ "Function like gap junctions" in animals.

◦ Allow passage of ions and larger molecules (signaling molecules, RNAs, transcription factors, viruses) between cells.

◦ Reduce electrical resistance between adjacent cells.

◦ Mostly formed during cell division.

Conclusion

The elaborate systems of cell adhesions, junctions, and extracellular matrices are fundamental to the existence and complexity of multicellular organisms. In animals, these structures facilitate cell-cell communication, maintain tissue integrity, and enable responses to mechanical stress. In plants, the rigid cell wall provides crucial structural support and protection, while plasmodesmata ensure intercellular communication. Understanding these sophisticated molecular architectures is vital for comprehending normal physiological processes and for addressing various diseases that arise from their dysfunction.