Post on 22-Feb-2016
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Cellular receptorsBy Poppy and Jake
Intracellular receptorsWhere are they?
What binds to them?
Intracellular (duh)Some are in the cytoplasm and some are in the nucleus.
Lipophillic and hydrophobic ligandsE.g. Steroids (sex and cortico)Small molecules, such as NO
Steroids Sex steroids AND corticosteroids.
- Testosterone- Oestradiol (oestrogen)- Cortisol- Progesterone- Aldosterone- And many more!
So some examples of steroids are…
SteroidsWhat are steroids made from?
Cholesterol!
NO• Viagra – works via the NO pathwayNO• NO is a small gas molecule, and simply moves across the cell
membrane.• It binds to its receptor (which is also an enzyme) on guanylate cyclase
and causes multiple downstream effects that lead to vasodilation.
- Guanylate cyclase converts GTP into cyclic GMP.
- cGMP activates protein kinase G (among other things)
- PKG phosphorylates myosin light chain kinase
- This leads to phosphorylation of the myosin light chain, leading to muscle relaxation
Ion channel receptors• Types of gating• Neuromuscular Junction (nAChR)
So how might they be gated?
• Voltage-gated channels (changes in membrane potential)• Channels for Na+, K+ and Ca2+
• Ligand-gated channels• Extracellular ligands - neurotransmitters
• Excitatory transmitters open Na+/K+-channels (depolarisation)• Inhibitory transmitters open Cl- channels (hyperpolarisation)
• Intracellular ligands - second messengers• cAMP (olfaction), cGMP (phototransduction), Ca2+
• Mechanically-gated channels (sound, touch, stretch)
Acetylcholine (nicotinic receptor) – Neuromuscular
Junction
The Neuromuscular Junction1. Action potential travels down
axon to NMJ
2. Depolarisation opens voltage-gated Ca2+ channels
3. Influx of Ca2+ causes exocytosis of ACh vesicles
4. ACh travels across the synaptic cleft and binds nicotinic Ach receptors which open.
5. Na+ moves into the motor end plate, through nAChR, propagating the action potential.
Receptors with intrinsic enzyme activity• Transmembrane protein• Exoplasmic domain binds ligand• Cytoplasmic domain has catalytic activity
• Binding of ligand activates the enzyme• Converting substrate to product (e.g. by phosphorylating)• The product changes cell behaviour
RTKs – Growth factors
RTK and Growth Factors
PP PP
Growth factor
1
Receptors
2 3
4GDP
GDPGTPadaptor Ras
Membrane
GTP
1. The growth factor binds to its receptor at the cell surface, which induces receptor dimerisation
2. Dimerisation triggers phosphorylation of receptors
3. Adaptor and Ras-GDP bind to phosphorylated receptors
4. Nucleotide exchange generates activate Ras-GTP
Imatinib (Gleevec)Inhibits tyrosine kinases,
preventing signalling cascade
Used to treat cancers
Receptors linked to soluble protein kinases• Remember that several other receptors fall under this! Including
receptor tyrosine kinases.• We will cover the JAK STAT pathway as the example one.
JAK STAT pathway
Erythropoeitin!
So what is the main importance of the JAK STAT pathway that you have covered so far?
EPO acts by binding to the erythropoietin receptor on proerythroblasts, activating the JAK STAT pathway. It works by preventing apoptosis on the proeryhtroblasts, leading to an increase in circulating erythroblast numbers.
Thanks for comingAny questions?