Topic 3: Cell Surface Molecues

• Extracellular Matrix Molecules


  • Proteoglycan
  • Hyaluronan
  • Collagen
  • Elastin
  • Fibronectin
  • Laminin
  • Integrin

  
• Extracellular Matrix (ECM)


  • Water-hydrated gel
  • Fibrous structural proteins that connect ECM to integrin and cells

  
• Organisation of Extracellular Matrix (ECM)

  Basal Membrane

  
• Components of Extracellular Matrix (ECM)


  • Provide framework for fibrous proteins
  • Compressive resistance
  • Lubrication
  • Tensile strength and recoil

  
• Functions of ECM


  • Mechanical Support
  • Cell anchorage and cell migration
  • Maintain cell polarity
  • Control of Cell Proliferation
  • Scaffolding for tissue renewals
  • Establishment of tissue microenvironments

  
• Integrins


  • Primarily cell-matrix adhesion but also in some cell-cell adhesions
  • Homologous transmembrane cell-matrix adhesion receptor

  
• Structure of Integrins


  • Alpha subunit and beta subunit
  • Forms a groove
  • Binds ECM with low affinity
  • Binding is Ca2+ / Mg2+ dependent
  • Bind with actin/filament
  • Integrin is cell-specific → large family

  
• Regulation of Integrin Activity

  1. Integrin binding usually lead to formation of focal complex

  2. Control is achieved by "inside-out signalling"

  3. Regulation is rapid because no de novo synthesis is needed

  4. Inactive form of integrin already synthesised and situated on membrane

  
• Selectins


  Circulating cells and endothelial cells, "rolling" adhesion

  
• Immunoglobulin superfamily cadherens


  Important in immune response, adherens junctions
• Cell – Cell Junction

  • Adhesion Junction
  • Adherens junction
  • Desmosome
  • Tight Junction
  • Communication Junction
  • Cell – Matrix Junction
• Adhesion Junction


  Linking cells by binding to actin (adhesion belt)
• Adherens Junction


  • Found in most multicellular organisms
  • Response to pulling force
  • Coordinate actin movements
  • Affect cell shape and orientation
  • Coordinate tissue remodelling

  
• Desmosomes


  • Found in vertebrates only
  • Linking cells by binding to the intermediate filament
  • Forming a 3D network of intermediate filament
  • Provide mechanical strength to epithelial cells

  
• Cadherin Family


  • Major junction molecules (CAM)
  • Multiple domain
  • EC → Extracellular Domain
• Features of Cadherin Superfamily

  • Calcium dependent (Cadherin)
  • Usually homophilic binding instead of heterophilic binding
  • Symmetrical anchoring junctions
• Tight Junction


  • Forming seal between cells
  • Separating fluid on the two sides of a cell
  • Provide selective permeability
  • A fence of the plasma membrane
• Gap Junction


  • Forming communication channel between two cells
  • Linking the cytoplasm between two cells
  • Allow passing of small water-soluble molecules
  • Signalling between two cells mediates by Ca2+ concentration and pH
• Structure of Gap Junction

  • Connexins (multiple members)
  • Six connexins form one hemichannel (connexon)
  • Multiple connexon aggregate and form a molecular sieve
  • Different members of connexins provide different selectivity and permeability
• Cell Surface Marker


  • Multicellular organisms consists of different types of cells
  • Each cell types consists of one / many unique cell surface molecules
  • The cell surface molecules usually related to the specific function of the cell
  • Vertebrates also needs to distinguish self and non-self cells/organism