Cellular receptorsBy 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 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…

Steroids

What 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 Junction

1. 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

GDPGTPadaptorRas

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?