Cellular receptors By Poppy and Jake

Intracellular receptors Where are they? What binds to them? Intracellular (duh) Some are in the cytoplasm and some are in the nucleus. Lipophillic and hydrophobic ligands E.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…

Steroids What are steroids made from? Cholesterol!

NO Viagra – works via the NO pathway NO 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 Junction 1.Action potential travels down axon to NMJ 2.Depolarisation opens voltage- gated Ca 2+ channels 3.Influx of Ca 2+ 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 GDP GTP adaptor 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 coming Any questions?