Cell Signalling


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Cell Signalling

  1. 1. Cell Signaling Molecules <ul><li>Cell-cell recognition </li></ul><ul><li>Although cells can act as self-contained units, they don’t exist in isolation </li></ul><ul><li>Even a unicellular organism must detect and respond to outside influences e.g. chemicals , light and other cells </li></ul><ul><li>In a multicellular organism, the organisation of tissues and systems brings more complexity </li></ul><ul><li>Therefore, it is essential that cells can COMMUNICATE to enable their activities to be fully coordinated </li></ul>
  2. 2. <ul><li>Communication involves transmitting and receiving information </li></ul><ul><li>A SIGNALING cell sends a signal and is received by a TARGET cell </li></ul><ul><li>[ S ignal molecules can induce different responses in their target cells e.g. acetylcholine : causes cardiac muscle to relax, but skeletal muscle to contract ] </li></ul><ul><li>If a change in the form of a signal is required, it is called a SIGNAL TRANSDUCTION </li></ul>Analogy: Faxing a letter – conversion of a printed form of information into an electronic form – back into a printed form ANIMATION
  3. 3. Communication Systems Signal molecules in the plasma membrane of the signal cell interact with membrane bound receptors on the target cell. These signals are therefore restricted to cells which are in direct contact CONTACT DEPENDENT Nerve cells or neurones elicit responses by the release of a neurotransmitter at synapses. Can signal over very long distances via a network of nerve cells. Very fast signalling e.g. GABA (Gamma-Amino-Butyric-Acid – an inhibitory neurotransmitter) NEURONAL Secretion of a local mediator. This affects cells in the immediate area of the signalling cell e.g. Histamine PARACRINE Secretion of a hormone into the bloodstream for dispersal. The signalling cell and the target cell can be far apart. Very slow method e.g. Insulin, Adrenaline ENDOCRINE
  4. 5. Extracellular HYDROPHOBIC Signaling Molecules <ul><li>Some small hydrophobic molecules can cross the plasma membrane and enter the cell by diffusion </li></ul><ul><li>Best known classes are the STEROID hormones e.g. cortisol & testosterone and the THYROID hormones e.g. thyroxine </li></ul><ul><li>The hormones can diffuse across the plasma membrane and bind to receptor proteins that are located either in the cytosol or in the nucleus itself </li></ul><ul><li>They work by activating GENE REGULATORY PROTEINS in the cell, which stimulate transcription of particular sets of genes in the nucleus </li></ul>
  5. 6. The mode of action of cortisol: Cortisol is a steroid hormone that is released in the body in response to physical or psychological stress. The secretion of cortisol induces energy-directing processes for the purpose of providing the brain with sufficient energy sources that prepare an individual to deal with stressors. In addition to its role as a so-called &quot;stress hormone&quot;, cortisol plays many key roles in almost every physiologic system. Regulation of blood pressure, cardiovascular function, carbohydrate metabolism, and immune function are among the best known functions of cortisol. <ul><li>Action of Cortisol animation [Diagram] </li></ul>
  6. 7. Extracellular HYDROPHILIC Signaling Molecules <ul><li>In contrast to the hydrophobic signals, the majority of signaling molecules are either too LARGE or too HYDROPHILIC to cross the plasma membrane </li></ul><ul><li>The receptor proteins for these signals must therefore present a binding site to the extracellular environment and elicit a response in the cytosol </li></ul><ul><li>There are 3 main classes of these cell surface transmembrane receptors all of which bind extracellular signal molecules, but generate intracellular responses in DIFFERENT ways … </li></ul>
  7. 8. 1) ION-CHANNEL LINKED Receptor <ul><li>These are also known as chemically-gated ion channels </li></ul><ul><li>They open pores through the protein in response to binding of a signal molecule </li></ul><ul><li>Ions flow through this ’gate’ generating an electrical effect </li></ul><ul><li>This type of receptor is found in excitable cells such as nerve and muscle cells </li></ul>
  8. 9. <ul><li>A neurotransmitter ( e.g. acetylcholine , noradrenaline ) binds to this type of receptor, altering its conformation to open or close a channel (often through or near the receptor) to the flow of Na2+, K+, Ca2+, or Cl- ions across the membrane. </li></ul><ul><li>Driven by their electrochemical gradient ( i.e. one side of the membrane has numerous ions, while the other side has few) the ions rush into or out of the cell, creating a change in the membrane potential due to the positive or negative nature of the ions. </li></ul><ul><li>This flow of ions through the channel can trigger a nerve impulse, or alternatively stop one from occurring. </li></ul>
  9. 10. 2) ENZYME LINKED Receptor <ul><li>Found in all types of cells </li></ul><ul><li>Generate an enzyme activity (usually a KINASE activity) on the cytoplasmic end of the protein </li></ul><ul><li>This kinase activity causes the phosphorylation of other intracellular proteins, thereby activating them </li></ul>
  10. 11. 3) G-PROTEIN LINKED Receptor <ul><li>Activate a GTP-binding protein (the G-protein ) that sets off a chain of events in the cell </li></ul><ul><li>This group of receptors is the largest known, and many different signals and responses can be associated with G-protein activity </li></ul><ul><li>All have the same structural arrangement within the membrane – known as a seven-pass transmembrane protein </li></ul><ul><li>Several hundred types of receptor are known, which bind signals as diverse as peptide hormone, amino acids, fatty acids and neurotransmitters </li></ul>
  11. 12. <ul><li>On binding the signal, the G-protein is activated by the binding of GTP </li></ul><ul><li>This activated protein diffuses away from the receptor protein site and activates its target protein </li></ul><ul><li>This may be an ion-channel protein or an enzyme such as adenylate cyclase or phospholipase C These enzymes catalyse the formation of small molecules known as secondary messengers which trigger the intracellular response to the original signal transduction event to the cell surface. </li></ul><ul><ul><li>G-Protein animation </li></ul></ul>
  12. 13. The cyclic AMP (cAMP) signal transduction pathway <ul><li>Adenylate cyclase activity generates cyclic AMP (cAMP), phospholipase C generates Inositol Triphosphate (IP3) </li></ul><ul><li>Second messengers are important parts of the signal transduction pathway, and can have many different effects </li></ul><ul><li>An outline of the cAMP pathway is shown below: </li></ul><ul><li>[Insert cAMP pathway diagram] </li></ul>
  13. 14. Signal Transduction <ul><li>Very complex area ! </li></ul><ul><li>Signals can be of many different types and can act either by diffusing across the plasma membrane (such as STEROID HORMONES e.g. testosterone and NITRIC OXIDE ) or by interacting with a receptor protein on the cell surface </li></ul><ul><li>The variety of signals, receptors and responses means that the system of signal reception and transduction can generate very specific effects in different types of cell </li></ul>
  14. 15. <ul><li>The response of a cell to a signal can involve ion flow, activation of specific proteins, or changes in gene expression </li></ul><ul><li>These effects can be short-lived, as in the case of the generation of an action potential, or they may be permanent alterations that control the developmental fate of the cell </li></ul><ul><li>It is therefore clear that the idea of a cell as a self-contained unit is in fact very far from the reality of the situation - cells are constantly engaged in the exchange of information in the form of molecular signals and it is this that enables cells in multicellular systems to function in an integrated way. </li></ul>