MBC - Cell Signalling Flashcards
What is cell signalling for?
- Processing information
- Self-preservation
- Voluntary movements
- Homeostasis
What are the main 2 systems that provide lines of communication?
- Nerve fibres of CNS/PNS
2. Blood vessels of cardiovascular system
What are the differences in the means of communication?
Nerves are rapid/instantaneous
Blood is slow/versatile
How is action potential generated?
Influx of Na+
Efflux of K+
This bio-electrical current generates action potential
How does neurotransmitters get released from vesicles?
- Action potential arrives at presynaptic knob open voltage-gated Ca+ channels
- Influx of Ca+ bind to vesicles —> exocytosis
How neurotransmitters activate post-synaptic receptors?
NT bind to receptors in post-synaptic membrane and activate bio-electrical current
What are the 2 consequences of NT binding to post-synaptic membrane opening ion channels?
Depolarisation
Hyperpolarisation
What are the different receptors on post-synaptic membrane?
- 7 transmembrane G-protein coupled receptors
- voltage(ligand)-gated ion channels/ ionotropic receptors
- enzyme-linked receptors
What are the 4 main types of hormonal communication?
- Endocrine comm
- Paracrine comm
- Autocrine comm
- Communication between membrane receptors
What is an example of endocrine comm?
Physiological response to hypoglycaemia
(Glucagon secreted by a-cells stimulates glycogenolysis (glycogen breakdown to glucose) & gluconeogenesis (pyruvate to glucose) in liver - to increase BGL)
- insulin (increase glucose uptake, reduce glycogenolysis/glucogenesis)
- adrenaline
What is endocrine signalling?
Hormone travels in blood vessel to act on distant target cell
What is an example of paracrine comm?
Physiological response to hyperglycaemia
(Insulin secreted by B-cell acts on a-cell to reduce production of glucagon)
- nitric oxide produced by endothelial cell in blood vessel (vasodilation - septic shock)
- osteoclast activating factors produced by adjacent osteoblasts (bone formation)
What is paracrine signalling?
When hormone acts on an adjacent cell
What is an example of signalling between attached proteins?
IMMUNE SYSTEM
- Blood borne virus detected by antigen presenting cell (APC)
- APC digests pathogen and expresses class II molecules on surface (MHC)
- MHC interact with circulating T-cell receptor
- Hepatitis C
- HIV GP120 & CD4 receptor on T-cells
- Bacterial cell wall component & toll-like receptors on haematopoietic cell
- corona virus & ACE2
What is signalling between membrane attached protein?
Plasma membrane proteins on adjacent cells interacting with each other
What is an example of autocrine signalling?
Activated T-cell receptor (TCR) has IL-2 receptor on surface
Secretion of IL-2 from T-cell binds to own/adjacent IL-2 receptor
- Negative feedback responses - acetylcholine act on presynaptic M2-muscarinic receptors
- Growth factors on tumour cells acts on itself to cause mitogenesis
What is autocrine signalling?
Signalling molecule act on the same cell (itself)
What is Lupus?
Autoimmune disease
- distinguish by facial rash resembling butterfly wings across both cheeks
What is multiple sclerosis?
Demyelination of nerve cells in brain and spinal cord - disrupt signal transmission
What is myasthenia gravis?
Neuromuscular disease (autoimmune) antibodies destroy receptors at junction between nerve and muscle leading to skeletal muscle weakness
What is rheumatoid arthritis?
Autoimmune disorder - inflammation at joints due to antibodies attacking synovium
What are chemical messages/molecules referred as when they exert defect by binding to receptors?
Ligands
What is a second messenger?
Chemical messenger, that evokes an intracellular effect, which is separate from the receptors or ligand
What are the 4 categories of receptors?
- Ligand-gated ion channel (ionotropic) receptors
- G protein coupled receptors
- Enzyme-linked receptors
- Intracellular receptors
How do ionotropic receptors work?
- The ligand binds to receptor protein (ligand-binding domain)
- Conformational changes opens pore
- Ions move in/out of cell according to concentration gradient
What are some examples of ionotropic receptors?
Acetylcholine on skeletal muscle for muscle contraction
What ions go through ionotropic receptors?
Sodium, potassium, calcium
Why are G protein-coupled receptors known as 7 transmembrane receptors?
Channel protein goes through membrane 7 times
What does a G protein complex contain?
- alpha subunit
- beta-gamma subunit
- GDP molecule
A Heterotrimer
What are the difference between G(alpha) subunits - associated with signal transduction pathways?
- q/11: activates PLC (promote Ca+ release from stores + activate non-selective channels)
- s: activates AC (activates PKA)
- i/o: inhibits AC ( inhibits PKA)
Describe the activation of G protein.
- Ligand binding causes G complex to associate with close proximity receptor
- GDP phosphorylation into active GTP
- G(alpha) subunit + GTP dissociated from G(beta-gamma) subunit - both act as secondary messengers, binds to target protein
- Internal GTPase dephosphorylates GTP -> GDP
- G(alpha) subunit becomes inactivated, dissociates from target protein
- Subunits re-associate to form G complex
(Cycle repeats until ligand is unbound)
What is the structure of enzyme-linked protein?
One transmembrane domain; ligand-binding domain (outside), specialised enzyme (inside)
How do enzyme-linked receptors work?
- Ligands bind to several receptors
- Cause receptor clustering which activate enzyme within cytoplasm
- Enzyme phosphorylates receptor (activated), leading to signalling to activate other parts of cell
- Signal stops when phosphatase dephosphorylates receptor
What hormones and how do they bind to Intracellular receptors?
Steroid hormone are membrane permeable (hydrophobic, lipophilic)
What are Intracellular receptors?
Transcription factors - regular mRNA & protein synthesis
Where are the Intracellular receptors located? (Type I & II)
Type I - cytoplasm
Type II - Nucleus
How do type I Intracellular receptors work?
Type I receptors are linked with ‘heat shock proteins HSP’ - chaperone molecules
- Hormones bind to receptor, type I dissociate with HSP to from hormone-receptor complex
- Joins with another identical hormone-receptor complex to form a HOMODIMER
- Homodimer translocates to nucleus, binds to DNA (as TF)
How do Type II intracellular receptors work?
- Hormone ligand go through cell & nuclear cell membrane
- Bind to Type II (already bound to DNA)
- Cause transcription
What are some examples of G-protein coupled receptors?
Beta-1 receptor: Gs
M2 receptor: Gi
AT-1 receptor: Gq
What are some examples enzyme-linked receptors?
-ErbB receptors for cell growth, proliferation
Ligand: epidermal growth factor, transforming growth factor(beta)
- insulin receptor for glucose uptake
Ligand: insulin
What are some examples of intracellular receptors?
Type I - Glucocorticoid receptors for lowering immune response/ increase gluconeogenesis
Ligand: Cortisol/corticosterone
Type II - Thyroid hormone receptors for growth and development
Ligand: Thyroxine (T4), Triiodothyronine (T3)
