Cell Signalling Flashcards
Why do we need cell signalling? List 4 things
- To process information - sensory stimuli
- For self preservation - from threatening stimuli, eg spinal reflex arc, sympathetic nervous system
- For voluntary movement - to perform daily tasks. Involves sensory and motor organs, coordinated by brain.
- For homeostasis - preserve cellular environment. Thermoregulation, glucose homeostasis.
What are the two main systems within the body that provide communication between the brain and the body?
What are the differences between these modes of communication?
- nerve fibres or the central and peripheral nervous system
- > nervous system provides a rapid, instantaneous response
-the blood vessels of the cardiovascular system
—> blood vessels provide slower more versatile regulation
- blood vessels provide transportation for blood cells and hormones (chemical messengers)
What are the steps involved in neurotransmission?
- Propagation of the action potential (AP)
- AP is propagated by VGSCs opening
- Na+ influx —> membrane depolarisation —> AP moves along neurone
- VGKC opening -> K+ effluent -> repolarisation - Neurotransmitter (NT) release from vesicles:
- AP opens voltage gated Ca2+ channels at presynaptic terminal
- Ca2+ influx -> vesicle exocytosis - Activation of postsynaptic receptors
- NT binds to receptors on post-synaptic membrane
- receptors modulate post synaptic activity
What are the 4 main modes of communication between hormones and receptors?
- Endocrine communication
- Paracrine communication
- Communication between membrane receptors
- Autocrine communication
What is endocrine communication?
What type of response is endocrine communication?
What is a process that uses endocrine signalling? Detail the steps involved.
Endocrine signalling - hormone travels within blood vessels to act on a distant target cell
Physiological response to hypoglycaemia involves endocrine communication
- > glycogenolysis
- > gluconeogenesis
Process:
- Glucagon is secreted by alpha cells of islets of langerhans (in pancreas)
- Glucagon travels out of pancreas in blood vessels
- Glucagon stimulates glycogenolysis and gluconeogenesis within the liver -> increasing blood glucose levels
Other e.gs: insulin produced in pancreas acts on the liver, muscle cells & adipose tissue
Adrenaline produced in adrenal glands acts on trachea
What is paracrine communication?
What is physiological response that uses paracrine communication? Detail the steps involved
What are some other examples of paracrine signalling?
Paracrine signalling - where a hormone acts on an adjacent cell
Hyperglycaemia- physiological response:
- glucose uptake
- reduced glycogenolysis
- reduced gluconeogenesis
Process: increased blood glucose -> insulin secreted by beta cells in the islets of langerhans
-insulin has paracrine effects: inhibits glucagon secretion by alpha cells. Insulin also has endocrine effects on the liver
Other e.gs:
- Nitric oxide produced by endothelial cells in blood vessels
- osteoclast activating factors produced by adjacent osteoblasts
What is communication between membrane receptors?
Give an example of when this type of communication is used
Signalling between membrane attached proteins: plasma membrane proteins on adjacent cells interacting
- Blood borne virus -> detected within blood stream by antigen presenting cell (APC)
- APC digests pathogen -> expresses major histocompatibility (MHC) class II molecules on surface
- Circulating T-lymphocyte engages with MHC molecule through T cell receptor (TCR) interaction
Other e.gs:
- HIV GP120 glycoprotein -> CD4 receptors in T-lymphocytes
- Bacterial cell wall components -> toll like receptors on haematopoietic cells
What is autocrine communication?
Give an example of autocrine signalling being used
Autocrine signalling: signalling molecule acts on same cell
E.g.
- activated TCR initiates 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:
- > binds to IL-2 receptor on same cell
- > binds to IL-2 receptor on adjacent activated T cell
Other egs.
- acetylcholine -> presynaptic M2 - muscarinic receptors
- growth factors (e.g. TGFbeta) from tumour cells -> mitogenesis
What are the 4 different types of receptors?
- Ionotropic receptor
- G protein coupled receptor
- Enzyme linked receptor
- Intracellular receptor
How do ionotropic receptors work?
(3 steps)
What is an example of an ionotropic receptor?
List: ligand, location and physiological effect
Ionotropic receptors signal transduction 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
Ionotropic receptor example: Nicotinic acetylcholine: Ligand: acetylcholine Location: skeletal muscle Physiological effect: muscle contraction
How do G-protein couples receptors work? (7 steps)
How are they activated and inactivated? Name receptors, enzymes and substrates involved
Signal transduction events:
- 7 TM receptor & heterotrimeric G-protein are inactive
- Ligand binding to receptor —> changes conformation of receptor
- Unassociated G-protein binds to the receptor -> bound GDP molecule is phosphorylated to GTP
GDP exchanged for GTP - G protein disassociates into two active components:
- alpha subunit
- beta subunit
- > each subunit binds to its target protein - Internal GTPase activity on alpha subunit dephosphorylates GTP -> GDP
- Alpha subunit dissociates from target protein -> becomes inactive again
- Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
How does the Gs protein linked receptor stimulate adenylyl cyclase?
How does the Gi protein linked receptor inhibit adenylyl cyclase?
How does the Gq protein linked receptor stimulate phospholipase C (PLC)?
- Gs protein linked receptor stimulates adenylyl cyclase:
-converts ATP to cAMP
-cAMP activates protein kinase A (PKA)
E.g. beta adrenergic receptor - Gi protein linked receptor inhibits adenylyl cyclase
- reduces levels of PKA - Gq protein linked receptor stimulates PLC
- converts PIP2 to IP3 and DAG
- IP3 stimulates Ca2+ release
- DAG activates PKC
How do enzyme linked receptors work?
- Ligand binds to receptor -> receptors cluster
- Receptor clustering activates enzyme activity within cytoplasmic domain
- Enzymes phosphorylate receptor
- Phosphorylation -> binding of signalling proteins to cytoplasmic domain
- These signalling proteins -> recruit other signalling proteins -> signal is generated within cell
What is an example of an enzyme linked receptor?
Name ligands and physiological effects
Insulin receptor (CE220 antigen)
Ligand: insulin
Physiological effect: glucose uptake
ErbB receptors
Ligand: epidermal growth factor, transforming growth factor beta
Physiological effect: cell growth, proliferation
What are the two types of intracellular receptors and how do they work?
Type 1 - cytoplasmic:
- Located within the cytosolic compartment
- Associated with chaperone molecules (heat shock proteins, hsp)
- Hormone binds to receptor -> hsp dissociates
- 2 hormone bound receptors form a homodimer
- The homodimer translocates to the nucleus -> binds to DNA
Type 2 - nuclear:
- Located within the nucleus
- Binding of hormone ligand -> transcriptional regulation
