L1 - Overview of cell signalling

• Cell to cell communication is also called cell signalling
• Cell signalling is a multistep process
• Cell Signalling/Intercellular Communication → signal send message to target cell

  1. Synthesis of signal molecule
  2. Release of signal molecule
  3. Transport of signal molecule to target detection of signal (reception) by target cell
  4. Response by target cell
  5. Some form of feedback - (that) signal has been received
• Intercellular Communication:

  • The chemical nature of the signal is very varied
  • Steroid, amino acid, amine, gas, peptide, protein
  • But the key factor as to how it works is weather it is lipid or water soluble
• Water Soluble signal molecule:

  • Can be stored in lipid vesicles within the signalling cell
  • Allow rapid release via exocytosis
  • Can travel in blood without a carrier
  • Can’t enter target cell
  • Because of phospholipid bilayer (not water soluble)
  • Message transduced via cell surface receptor
  • Eg neurotransmitters, peptides
• Lipid Soluble signal molecule:

  • Can’t be stored as leaks across membrane
  • Made on demand (slow response)
  • Has to make & release it
  • Travels in blood w/ a carrier protein
  • Blood = water environment, not chemically compatible
  • Can enter target cells by crossing their membrane
  • Cross & enter to do stuff
  • Acts on intracellular receptors often to directly regulate gene expression
  • Eg steroid, testosterone
• Juxtacrine Cell signalling:

  • Requires direct cell to cell contact
  • Mediated by gap junctions composed of proteins call connexins
  • Allows ions & small molecules to move between cells
  • Gap junctions are bi-directional
  • Provide electrical & chemical coupling between cells
  • Allow very rapid communication between groups of cells
  • Eg cardiac muscle cells or groups of neurons
  • Specificity achieved by direct contact (specific receptor for specific signal)
• Gap junction can only talk to cell next to it
• Cells right next to each other, junctions connect cells, don’t have to send message out of cell they communicate through gap junctions
• Juxtacrine Cells signalling:

  • Juxtacrine signalling can involve receptors
  • But the signalling molecule is not / never released
  • Eg the notch pathway
  • Can deliver more complex info than gap junction
  • Specificity achieved by receptor expression & direct contact
  • Controls how cells divide
  • Development of organisms
• Cells signalling occurs in multiple modes
• Autocrine Cells signalling:

  • Signalling between nearby cells of the same type
  • Requires the release & detection of signal molecule
  • Group release signal at same time
  • Can coordinate activity between a group of similar cells
  • Specificity achieved by selective receptor expression & rapid degradation of signal molecule
• Paracrine Cell signalling:

  • Local signalling bw/ different cell types
  • Requires the release & detection of signal molecule
  • Eg endothelial cells communicate w/ nearby vascular smooth muscle via the release of nitric oxide - of major important in blood pressure regulation
  • Specificity achieved by selective receptor expression & rapid degradation of signal molecule
• Paracrine Cell signalling:

  • Specificity → when signal release, muscle cells have selective receptor, what if travelled further down vessel - it’s degraded very quickly so can’t act on cells further away as is LOCAL
• Endocrine Cells signalling:

  • Often involves signalling between distant cells
  • Chemical signals called hormones carried in the blood
  • Hormones produced from discrete endocrine glands, endocrine tissues & isolated cells
  • Hormones are of multiple chemical types (steroids, modified amino acids, peptides)
  • Specificity achieved by selective receptor expression
• Neuronal Cells signalling:

  • Signalling molecules (neurotransmitter) released from neurons at specialised highly localised synaptic sites
  • Neurotransmitters are of multiple chemical types (amino acids, amines, peptides)
  • Cause rapid & often short-lasting effects
  • Specificity achieved by precise contacts & rapid removal of neurotransmitter to prevent diffusion
• Neuroendocrine Cells signalling:

  • Neurotransmitter released from neurons into the blood
  • Important in the regulation of the endocrine system
  • Hypothalamic neurons project to the posterior pituitary to control hormone (ADH & oxytocin) release into the systemic circulation
  • Other hypothalamic neurons control hormone release from the anterior pituitary
  • Neuroendocrine cells in the adrenal medulla release catecholamines into the blood in response to stress
• Different ways of specificity:

  • Receptors
  • Anatomically targeted (synapse - neural)
  • Signal degradation
• What response could the signal cause in the cell:

  • Grow - cell division
  • Divide - replacement, repair & growth
  • Mitosis
  • Die (cell death)
  • Change form (differentiate) = change shape
  • Become active (do something)
  • Contract
  • Move
  • Fire an action potential (AP)
  • Release a signal of its own
  • Make more of something
  • Breakdown something
• How do these effects occur:

  • Receptor activation by a signal may change the amount or the activity of specific proteins which then mediate an effect
  • Alter the gene expression of specific proteins
  • Alter the activity of specific proteins
  • Cell signalling often does both
• Effects:

  1. If want signal to change that, send signal to gene turns it on, makes more (amount) of protein so can have more of that

  2. Protein not made in active form sometimes, turn it on or off, change activity
• Specificity = only wants to affect specific cells, only those that have the receptor