Cell Signalling Flashcards
Why do cells need to communicate?
1. Process Information Sensory stimuli - e.g. light 2. Self Preservation - protection from danger Spinal reflexes Sympathetic nervous system 3. Voluntary Movement 4. Homeostasis Thermoregulation Glucose homeostasis
What are the 4 types of cell signalling.
- Endocrine signalling
- Paracrine signalling
- Signalling between membrane attached proteins
- Autocrine signalling
What is endocrine signalling?
Intercellular type of signalling
Hormones used to communicate - travels via the blood and acts on a distant target cell
What is hypoglycaemia?
Low blood sugar (glucose) levels
How does the body regulate hypoglycaemia?
Glucagon is secreted by the alpha cells in the islets of Langerhans
Stimulates gluconeogenesis and glycogenolysis in the liver
What are some other examples of endocrine cell signalling?
Adrenaline - fight or flight (increasing breathing and heart rates)
Insulin - produced by the beta cells in the islets of Langerhans in the pancreas, which act on the liver, muscle cells and adipose tissue
What is paracrine signalling?
Hormones acting on adjacent cells
What is hyperglycaemia?
High blood sugar levels
How is hyperglycaemia regulated?
Insulin is secreted by the beta cells in the islets of Langerhans (pancreas)
It has endocrine effects: stimulates glucose uptake
It also has paracrine effects: It inhibits glucagon secretion by nearby alpha cells
What are some other examples of paracrine signalling systems?
Nitric oxide - prevents the contraction of the smooth muscle in blood vessel and so acts as a vasodilator
What is signalling between membrane attached proteins?
Plasma membrane proteins on adjacent cells binding together/interacting
What are some examples of signalling using membrane attached proteins (i.e. glycoproteins)?
E.g. immune system - when blood borne viruses are detected and engulfed by antigen presenting cells (APCs), which digests the pathogen and expresses the antigens on its cell surface so circulating T cells can bind.
HIV - glycoproteins bind to CD4 receptors on T cells, used to get into cells
Bacterial cell wall components bind to toll-‐like receptors on haematopoietic cells
Coagulation is platelet receptors attaching together
What is autocrine signalling?
Signalling molecule acts on same cell - i.e secreted by a cell and acts on itself
Used for feedback loops
What are the 4 types of post synaptic receptors?
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What are some examples of autocrine signalling?
Activated T-cell receptor (TCR) will initiate a cascade of reactions within T-cell
Activated T-cell expresses interleukin-2 (IL-2) receptor on surface
Activated T-lymphocyte also secretes IL-2, which:
1. Binds to IL-2 receptor on same cell
2. Binds to IL-2 receptor on adjacent activated T-cell
[ Acetylcholine binds to pre‐synaptic muscarinic receptors (negative system)
Growth factors from tumour cells can lead to mitogenesis in the tumour cell ]
What are the 4 types of post synaptic receptors?
Ligand and neurotransmitters are the same thing!
- Ionotropic Receptor ‐ ligand binding opens an ion permeable pore
- G-protein coupled receptor ‐ ligand binding activates intracellular G ‐ protein•Enzyme linked receptor-‐ligand binding leads to receptor clustering which activates internal enzymes•Intracellular Receptor-‐a membrane permeable ligand binds to a receptor inside the cell
How does the ionotropic receptor work? [Signal Transductional Events]
Ligand binds to the receptor protein
Change in conformation of channel protein, opening of a pore
Pore allows ions to move in or out of cell according to their respective concentration gradients
What are some examples of ionotropic receptors?
E.g. Nitcotinic acetylecholine receptor - located on skeletal muscle at neuromuscular junctions, acetylcholine binds, and it begins the depolarisation which leads to muscle contraction
GABA - Located on many cells in the CNS, allows transmission of anions. GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride ions, causes a depression activity. If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures
How does the G-protein coupled receptor work? [Signal Transductional Events]
GPCR is also called 7-TM (7 transmembrane)
G-protein exists as a heterotrimer - 3 subunits, alpha, beta and gamma
Ligand binding causes conformational change of the receptor
Allows unassociated G-protein to bind to the internal surface of the GPCR
GDP is exchanged for GTP
GTP provides energy for G-protein to dissociate into two active components: alpha and beta-gamma
Both bind to their target cells respectively
Once the alpha subunit has attached to the target protein, internal GTPase activity within the subunit causes the GTP molecule to change to a GDP molecule
Allows the alpha subunit to unbind from the target protein and reform the heterotrimer with GDP attached
How long does the G-protein coupled receptor stay active?
As long as ligand is bound and can activate further heterotrimeric G-proteins
What are the 3 types of G-alpha subunit linked receptor?
1. Gs protein linked receptor S = stimulatory 2. Gi protein linked receptor i = inhibitory 3. Gq protein linked receptor
How does the Gs protein linked receptor work?
Stimulates adenylate cyclase
Adenylate cyclase converts ATP to cAMP
cAMP increases levels of PKA (protein kinase A)
Example: β1-adrenergic receptor (found on the heart)
NOTE: beta blockers act on the β1-adrenergic receptor
How does the Gi protein linked receptor work?
Opposite effect to the Gs protein
Inhibits adenylate cyclase thus reducing levels of cAMP and PKA
Example: M2-muscarinic receptor
How does the Gq protein linked receptor work?
Activates phospholipase C (PLC)
PLC converts PIP2 (Ohosphatidylinositol Bisphosphate) —-> IP3 + DAG
IP3 —> increase in intracellular Ca2+
DAG (Diacylglycerol) - activates PKC
Example: AT-1 angiotensin receptor (Angiotensin is a hormone produced in the kidneys which is the most potent vasoconstricter in the body)
