adhesion and junction

• Cell Junctions and Adhesion

  Introduction to cell junctions, cell adhesion mechanisms, and the extracellular matrix
• Cell Junctions and Adhesion

  • Cell-cell and cell-extracellular matrix adhesion is essential to build multi-cellular organisms
  • There are various types of cell-cell and cell-ECM junctions
  • Cell-cell and cell-ECM junctions require transmembrane proteins and links to the cytoskeleton
• Cell Junctions and Adhesion

  • Cell cohesion affects seemingly static processes like cell and tissue shape and arrangement
  • Cell cohesion to other cells and ECM generates strength and elasticity
  • Cell cohesion is responsible for effecting dynamic processes like creating pathways for communication and exchange
• Types of tissue


  • Connective (bone and tendon)
  • Epithelial (lining of gut and skin)
• Classes of cell junctions and their functions

  • Anchoring junctions: cell-cell and cell-ECM adhesion transmit stress and tether to cytoskeleton
  • Occluding junctions: seal gaps between cells in epithelia; tight junctions are impermeable
  • Channel-forming junctions: allow passage of content between connected cytoplasm
  • Signal-relaying junctions: neuronal synapses and juxtacrine signaling
• Transmembrane proteins (TM)


  • Form adhesion contacts by acting like adaptors: link the cytoskeleton to extracellular ligands
  • Extracellular ligands include extracellular domains of other TM proteins (cell-cell adhesion) or ECM components
• Superfamilies of transmembrane proteins

  • Cadherin superfamily mediate cell-cell adhesion
  • Integrin superfamily usually control cell-matrix contact
• Cadherins


  A large family of cell-cell and cell-ECM adhesion proteins that mediate homophilic interactions
• Cadherins


  • Recognized by the cadherin domain/motif
  • Ca2+ binds to cadherin domain/motif to unfold the protein, allowing N-terminal tips of cadherins on opposing cells to bind in trans
  • Forms a molecular velcro that holds cells together
• Classical cadherins


  • E-cadherin
  • N-cadherin
• Homophilic binding


  Cell adhesion molecules bind to like molecules on neighbouring cells
• Heterophilic binding


  Cell adhesion molecules bind to unlike molecules on neighbouring cells
• Cadherins exhibit homophilic binding
• Calcium (Ca2+)


  Essential for the conformation of the interlocking motifs in cadherin homophilic binding
• Adherens junctions


  Cadherins bind to the actin cytoskeleton to form permeable junctions
• Catenins


  Adaptor proteins that link cadherins and the actin cytoskeleton
• Maturation of the adherens junction

  1. Intercellular cadherin interactions start with small clusters and mature into long, zippering clusters that assemble actomyosin cables

  2. Builds contractile actin rings around epithelial cells that protect and give strength to tissue
• Adherens junctions


  • Join the actin cytoskeleton between cells to strengthen tissue
  • Form the adhesion belt that builds the actin rings around cells and connects cell-to-cells
  • Are anchoring junctions, different from tight junctions
• Tight junctions


  Seal gaps between cells in epithelia to create an impermeable barrier
• Tight junctions


  • Formed by trans and cis-interactions between occludins and claudins
  • Disruption causes fluid loss and potential death
• Epithelium tissue


  • Creates a boundary between organism and non-living world and/or delineates specific organs/tissues
  • Generates a selective permeability barrier
  • Polarized: basal is anchored, apical is free
• Intestinal epithelium


  • Consists chiefly of absorptive epithelial cells specialized for nutrient uptake
  • Apical membrane has active transporters, basal membrane has passive transporters
• Tight junctions


  • Form a seal that separates apical from basolateral extracellular space
  • Stop diffusion, preventing loss of salts and nutrients by epithelia
• Tight junction strands


  • Composed of multimerized claudin and occludin proteins
  • Claudin and occludins are transmembrane proteins expressed in epithelial cells
• Electron-dense tracers


  Added to apical vs. basolateral side of cells - cannot diffuse across
• Tight junctions


  • Consist of "sealing strands" that completely encircle each epithelial cell
• Tight junction seal


  • Stronger with increased number of parallel sealing strands
• Sealing strands


  Consist of multimerized claudin and occludin proteins
• Claudin and occludin


  • Transmembrane proteins expressed in epithelial cells
  • Interact in cis (same cell) and in trans (between cells) to form and zip strands
• Claudin-1 knockout mice


  • Die from dehydration due to defects in skin epidermis
  • Have very wrinkled skin and died within 1 day of birth
  • Suffer from massive weight loss within ONE day
• Transepidermal water loss assay


  Measures direct vapour from dorsal skin
• Gap junctions


  • Cell-cell links that form pores connecting intercellular cytoplasm
  • Allow for small molecules to permeate between cells like Ca2+
• Connexons


  • Hexamer rings of connexins that bind in trans across cells
• Gap junctions


  • Essential to synchronize tissue-wide events like heart beating, peristaltic intestinal movements, hearing and vision
• Gap junctions


  • Allow passage between cells of molecules <1000 Da
  • Allow cells to communicate with neighbours
• Gap junctions


  • Formed by many hexameric connexons
• Functions and diseases linked to gap junctions in animals

  • Electrically-excitable cells (neurons): permit the spreading of membrane potential changes (action potential)
  • Synchronization of cardiac muscle during heart beating and intestinal peristaltic movement controlled by smooth muscles
  • Mutations in connexin isoforms involved in infertility, deafness (most common cause of congenital deafness), neuronal disease
• Gap junction permeability regulation

  Can be opened and closed, e.g. damage can open or close gap junctions
• Extracellular matrix (ECM)


  • A meshwork of proteoglycans, polysaccharides, fibrous proteins and glycoproteins
  • Forms a substratum for cell adhesion and building tissues
• Proteoglycans


  Proteins conjugated to glycosaminoglycans that serve to fill-space, absorb forces and lubricate