Signalling Unit 1

• Co-ordination


  Multicellular organisms signal between cells using extracellular signalling molecules
• Signal Specificity


  Different cell types produce specific signals that can only be detected and responded to by cells with the specific receptor
• Signalling Specificity


  In a multicellular organism, different cell types may show a tissue-specific response to the same signal
• The mRNA is transcribed from DNA in the nucleus and translated into proteins by ribosomes in the cytoplasm
• mRNA


  The molecule transcribed from DNA that is then translated into proteins
• Translation is the next step after transcription
• RNA polymerase moves along DNA unwinding the double helix and breaking the hydrogen bonds between the bases. RNA polymerase synthesises a primary transcript of mRNA from RNA nucleotides by complementary base pairing
• Requirements of transcription/translation


  • DNA to act as template
  • Free RNA nucleotides
  • Enzymes including RNA polymerase
  • ATP
• Gene expression is controlled by the two processes called transcription and translation
• Transcription


  The process of making mRNA from the template provided on DNA
• What transcription needs


  • DNA to act as template
  • Free RNA nucleotides
  • Enzymes including RNA polymerase
  • ATP
• Transcription


  1. RNA polymerase moves along DNA unwinding the double helix and breaking the hydrogen bonds between the bases

  2. RNA polymerase then synthesises (copies) the DNA code which is called a primary transcript and is made of mRNA

  3. This is made from RNA nucleotides and uses complementary base pairing

  4. This all takes place in the nucleus
• RNA polymerase


  The enzyme responsible for transcription and unwinding the DNA, responsible for the synthesis of the mRNA molecule adding nucleotides to the 3' end until it reaches the end of the gene
• Primary transcript


  The resultant mRNA strand that becomes separated from its DNA template
• Hydrophobic


  Molecules that are seemingly repelled by a mass of water, also known as non-polar
• Hydrophobic signalling


  Hydrophobic molecules can diffuse directly through the phospholipid bilayers of membranes, and so bind to intracellular receptors
• Intracellular receptors


  These receptors are transcription factors
• Transcription factors


  Proteins that when bound to DNA can either stimulate or inhibit initiation of transcription
• Hydrophobic signalling molecules


  • Oestrogen
  • Testosterone
• Hydrophobic signalling


  1. Steroid hormones bind to specific receptors in the cytosol or the nucleus

  2. The hormone-receptor complex moves to the nucleus where it binds to specific sites on DNA and affects gene expression

  3. The hormone-receptor complex binds to specific DNA sequences called hormone response elements (HREs)

  4. Binding at these sites influences the rate of transcription, with each steroid hormone affecting the gene expression of many different genes
• Steroid receptor


  • Steroid hormone
  • Hormone-receptor complex
  • Complex binds to sites that activate mRNA transcription
• Hydrophilic


  A molecule that is attracted to water molecules and tends to be dissolved by water, also known as polar molecules
• Hydrophilic signals


  Hydrophilic signalling molecules bind to transmembrane receptors and do not enter the cytosol
• Hydrophilic extracellular signalling molecules


  • Peptide hormones
  • Neurotransmitters
• Transmembrane receptors


  Transmembrane receptors change conformation when the ligand binds to the extracellular face, the signal molecule does not enter the cell, but the signal is transduced across the plasma membrane
• Transduction


  The process by which a chemical or physical signal is transmitted through a cell by a series of molecular events resulting in a cellular response
• Hydrophilic signalling


  1. Transmembrane receptors act as signal transducers by converting the extracellular ligand-binding event into intracellular signals, which alters the behaviour of the cell

  2. Transduced hydrophilic signals often involve G-proteins or cascades of phosphorylation by kinase enzymes
• 1. proteins

  2. Proteins relay signals from activated receptors (receptors that have bound a signalling molecule) to target proteins such as enzymes and ion channels
• Receptor


  • G-protein
  • Enzyme
• Phosphorylation cascades


  Phosphorylation cascades allow more than one intracellular signalling pathway to be activated, they involve a series of events with one kinase activating the next in the sequence and so on, phosphorylation cascades can result in the phosphorylation of many proteins as a result of the original signalling event
• Insulin signalling


  1. Binding of the peptide hormone insulin to its receptor causes a conformational change that triggers phosphorylation of the receptor

  2. This starts a phosphorylation cascade inside the cell

  3. This phosphorylation eventually leads to GLUT4-containing vesicles being transported to the cell membrane
• Diabetes mellitus


  Diabetes mellitus can be caused by failure to produce insulin (type 1) or loss of receptor function (type 2), type 2 is generally associated with unhealthy lifestyle choices
• Exercise


  Also triggers recruitment of GLUT4, so can improve uptake of glucose to fat and muscle cells in subjects with type 2 diabetes
• Nerve impulse


  A signal transmitted along a nerve fibre
• Resting membrane potential


  A state where there is no net flow of ions across the membrane
• Action potential


  A wave of electrical excitation along a neuron's plasma membrane
• Neurotransmitters


  Chemicals that transmit a signal across a synapse (gap between two neurons), neurotransmitters initiate a response by binding to their receptors (ligand-gated ion channels) at a synapse
• Depolarisation


  A sudden change in membrane potential - usually from a (relatively) negative to positive internal charge
• Depolarisation


  Ion movement occurs and there is depolarisation of the plasma membrane, if sufficient positive ion movement occurs, and the membrane is depolarised beyond a threshold value, the opening of voltage-gated sodium channels is triggered and sodium ions enter the cell down their electrochemical gradient and further depolarisation occurs
• Repolarisation


  A short time after opening, the sodium channels become inactivated, voltage-gated potassium channels then open to allow potassium ions to move out of the cell to restore the resting membrane potential, this leads to a rapid and large change in the membrane potential