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• Cells do not live in isolation
• Signalling


  Cells receive and act on signals from beyond their plasma membranes
• Signalling


  • Controls all aspects of cell behaviour e.g. growth, differentiation and development, metabolism
• Signalling defects


  Can have consequences for disease e.g. cancer, heart disease, diabetes, neurological diseases
• Signals


  • pH
  • Osmotic strength
  • Food
  • Oxygen
  • Light
  • Noxious chemicals
  • Predators
  • Competitors
• Bacteria have membrane proteins that act as information receptors
• Signal transduction


  1. Signal

  2. Receptor

  3. Response
• Signalling and responses are complex, but all follow the universal pattern: signal -> receptor -> response
• Agonists


  Ligands that stimulate pathways
• Antagonists


  Ligands that inhibit pathways
• Signalling cell


  Produces a signal
• Environmental stimulus


  Produces a signal
• Target cell


  Induces a response
• Ligands


  Signals (from the Latin ligare, to bind)
• Direct contact signalling


  • A protein (ligand) on the signalling cell binds a protein (receptor) on the target cell. The target cell responds.
• Gap junctions


  • Exchange small (< 1.2 kDa) signalling molecules and ions, co-ordinating metabolic reactions between cells
• Autocrine signalling


  • The ligand induces a response only in the signalling cell. Most autocrine ligands are rapidly degraded in the extracellular medium. Often used to enforce developmental decisions.
• Paracrine signalling


  • The ligand induces a response in target cells close to the signalling cell. Diffusion of the ligand is limited. It is destroyed by extracellular enzymes and internalised by adjacent cells.
• Endocrine signalling


  • The ligand is produced by endocrine cells and is carried in the blood, inducing a response in distant target cells. The ligands are often called hormones (from Gk: to set in motion).
• The distinctions between different types of signalling are not always absolute: some ligands can belong to more than one class
• Cell-type specific expression


  • Some receptors are only present on certain cells. Molecules downstream of the receptor are only present in some cells.
• Differential gene expression


  Genes can be turned 'on' or 'off' by interaction of positive (activators) and negative (repressor) regulators with enhancer or silencer control elements.
• High affinity interactions


  • There is a precise molecular complementarity between ligand and receptor, mediated by non-covalent forces (like enzyme-substrate and antibody-antigen interactions).
• Affinity


  The strength of the association between a ligand and its receptor
• Association rate


  Determined by the concentrations of both reactants (receptor and ligand) and by a constant k+
• The association rate is a rate of concentration change, so is in Ms-1 (molar per second)
• The association rate constant k+ has units of M-1s-1
• Complement


  Something that completes or brings to perfection
• Molecular complementarity


  A 'perfect' fit
• Specificity


  • Provided by two mechanisms: High affinity interactions
• Affinity


  The strength of the interaction between two molecules
• Interactors


  The receptor (R) and the ligand (L)
• Receptor-ligand binding


  R (receptor) + L (ligand) ⇌ RL (receptor-ligand complex)
• Association rate


  k+ [R][L]
• Association rate constant (k+)


  Has units of M-1s-1 (per molar per second)
• Receptor-ligand dissociation


  RL (receptor-ligand complex) ⇌ R (receptor) + L (ligand)
• Dissociation rate


  1. [RL]
• The dissociation rate is a rate of concentration change, so is in Ms-1 (molar per second)
• Dissociation rate constant (k-)


  Has units of s-1 (per second)
• Equilibrium constant (Keq)


  k+/k- = [RL]/[R][L], has units of M-1 (per molar)