Beyond the Cell: Cell Adhesions, Cell Junctions, and Extracellular Structures

Introduction

Multicellular organisms rely on specialized structures to organize cells into tissues and organs. These structures include cell adhesions, cell junctions, and extracellular matrices, which together provide mechanical strength, facilitate communication, and regulate cellular behavior.

Types of Tissues in Animals

Overview of Animal Tissues

• Epithelium: Sheets of polarized cells with distinct apical and basal domains, forming protective barriers and involved in absorption and secretion.

• Connective Tissue: Loosely organized cells embedded in an extracellular matrix (ECM), providing structural support and connecting other tissues.

Cell-Cell Junctions

Types of Cell Junctions

• Adhesive Junctions: Anchor the cytoskeleton to the cell surface and mediate cell-cell adhesion.

• Tight Junctions: Seal adjacent cells to prevent the passage of molecules between them.

• Gap Junctions: Allow direct communication between cells via small channels.

• Plasmodesmata (plants): Cytoplasmic channels that traverse cell walls, enabling communication between plant cells.

Major Types of Cell Attachments in Epithelial Cells

Epithelial cells utilize a combination of adhesive, tight, and gap junctions to maintain tissue integrity and function.

Adhesive Junctions

• Anchor the cytoskeleton to the cell surface using specialized adhesion proteins.

• Mediate homophilic (identical receptors) and heterophilic (different receptors) interactions.

• Dynamic structures, assembled and disassembled in response to cellular events.

Types of Adhesive Junctions

• Adherens Junctions: Cadherin-mediated, connect to actin filaments.

• Desmosomes: Button-like points of strong adhesion, connect to intermediate filaments.

Cadherins and Associated Proteins

• Cadherins: Transmembrane proteins with extracellular repeats, mediate calcium-dependent cell-cell adhesion.

• E-cadherin: Prominent in epithelial cells, forms zipper-like interactions.

• β-Catenin and α-Catenin: Link cadherins to the actin cytoskeleton; α-catenin also binds vinculin for additional strength.

• p120 Catenin: Regulates cadherin stability and endocytosis.

Tissue specificity: Different cadherins are expressed in different tissues, influencing cell sorting and tissue formation.

Desmosomes

• Provide mechanical strength, especially in tissues under stress (e.g., skin, heart muscle).

• Composed of desmocollins and desmogleins (cadherin family), linked to intermediate filaments via plakoglobin, desmoplakin, and plakophilin.

Other Cell-Cell Adhesion Molecules

• Lectins: Carbohydrate-binding proteins that mediate cell-cell adhesion by binding specific sugars.

• Cell Adhesion Molecules (CAMs): Immunoglobulin superfamily proteins (e.g., N-CAM) mediating homophilic interactions.

• Selectins: Mediate leukocyte adhesion during inflammation; different types are expressed on leukocytes (L-selectin), platelets (P-selectin), and endothelial cells (E-selectin).

Tight Junctions

Structure and Function

• Seal epithelial cells together, forming a barrier to prevent the movement of molecules between cells.

• Composed of transmembrane proteins such as occludin, claudins, and junctional adhesion molecules (JAMs).

• Claudins form ion-selective pores for paracellular transport (movement between cells).

• Block lateral movement of membrane proteins and lipids, maintaining cell polarity.

Gap Junctions

Structure and Function

• Regions where plasma membranes of adjacent cells are closely aligned, connected by connexons (assemblies of six connexin proteins).

• Allow passage of small molecules and ions (up to ~1 kDa) but not proteins or nucleic acids.

• Enable direct electrical and chemical communication between cells.

• Invertebrates use innexins instead of connexins.

The Extracellular Matrix (ECM) of Animal Cells

Types and Functions

• Bone: Rigid ECM with few cells.

• Cartilage: Flexible ECM, mainly matrix materials.

• Connective Tissue: Gelatinous ECM with fibroblasts.

Classes of ECM Molecules

• Structural Proteins: Collagens (strength), elastins (flexibility).

• Protein-Polysaccharide Complexes: Proteoglycans (matrix formation).

• Adhesive Glycoproteins: Fibronectins and laminins (cell-matrix attachment).

Collagens

• Most abundant ECM protein; forms triple-helical fibers with high tensile strength.

• High glycine, hydroxylysine, and hydroxyproline content; stabilized by hydrogen bonds.

• Assembled as procollagen in the ER, processed extracellularly to form fibrils and fibers.

• Multiple types (at least 15), tissue-specific.

Elastins

• Provide elasticity; rich in glycine and proline, crosslinked by lysine residues.

• Allow tissues to stretch and recoil (e.g., skin, lungs).

Proteoglycans and Glycosaminoglycans (GAGs)

• Proteoglycans: Core proteins with covalently attached GAG chains.

• GAGs: Large, hydrophilic polysaccharides with repeating disaccharide units (e.g., chondroitin sulfate, keratan sulfate, hyaluronate).

• Form a gel-like matrix that embeds collagen and elastin fibers.

• Hyaluronate can exist freely and acts as a lubricant in joints.

Adhesive Glycoproteins

• Fibronectins: Bind cells to ECM, guide cell movement, and participate in blood clotting.

• Laminins: Major component of the basal lamina, bind cells to the ECM and provide structural support.

Integrins

• Transmembrane receptors composed of α and β subunits.

• Bind ECM components (fibronectin, laminin) and connect to the cytoskeleton via adaptor proteins (e.g., talin, vinculin, α-actinin).

• Mediate focal adhesions (actin-linked) and hemidesmosomes (intermediate filament-linked).

• Participate in signaling pathways (inside-out and outside-in signaling).

Specialized ECM Attachments

• Dystrophin/Dystroglycan Complex: Stabilizes muscle cell attachments to the ECM; mutations cause muscular dystrophies.

• Costameres: Structures aligning with Z-discs in muscle, containing dystrophin and linking the cytoskeleton to the ECM.

The Plant Cell Surface

Cell Walls

• Provide structural support and act as a permeability barrier.

• Composed of cellulose microfibrils, hemicelluloses, pectins, and glycoproteins (extensins).

• Lignins add rigidity and resistance to compression, especially in woody tissues.

Cell Wall Synthesis

• Middle Lamella: First layer, rich in pectins, glues adjacent cells together.

• Primary Cell Wall: Formed during cell growth, flexible and thin.

• Secondary Cell Wall: Deposited after growth, thick and rigid, rich in cellulose and lignin.

Plasmodesmata

• Cytoplasmic channels traversing cell walls, lined by plasma membrane, containing a central desmotubule.

• Allow passage of ions, signaling molecules, RNAs, and even viruses between cells.

• Functionally analogous to gap junctions in animal cells.

Summary Table: Major Cell Junctions and ECM Components

Key Terms and Concepts

• Cadherin: Calcium-dependent adhesion protein mediating cell-cell adhesion.

• Catenin: Cytoplasmic protein linking cadherins to the cytoskeleton.

• Integrin: Transmembrane receptor connecting ECM to cytoskeleton.

• Proteoglycan: Protein with covalently attached GAG chains, forming hydrated gels.

• Plasmodesma: Channel through plant cell walls for intercellular communication.

Formulas and Equations

• Collagen Triple Helix: Each collagen molecule consists of three α chains wound together:

• Glycosaminoglycan Repeating Unit:

Applications and Clinical Relevance

• Epithelial-Mesenchymal Transition (EMT): Involves changes in cadherin expression, important in development and cancer metastasis.

• Muscular Dystrophy: Caused by mutations in dystrophin, affecting muscle cell attachment to the ECM.

• Blood Clotting: Plasma fibronectin promotes platelet adhesion to fibrin during clot formation.

• Plant Growth: Expansins and auxin regulate cell wall flexibility during growth.

Additional info: Some explanations and clinical examples were expanded for clarity and completeness.