2.9 Cell Signaling Flashcards
What are the four reasons we need cell signalling?
- Process sensory stimuli
- Self preservation (e.g. spinal reflexes)
- Voluntary movement
- Homeostasis (e.g. thermoregulation, glucose homeostasis)
What is meant by self-preservation?
The activation of the reflex arc to protect ourself from danger
What are the two systems which provide the main lines of communication?
Nerve fibers of the central and peripheral nervous system
Blood vessels of the cardiovascular system
What line of communication is used for a rapid, instantaneous response?
The nerve fibres of the CNS and PNS
What line of communication is slower and more versatile?
The blood vessel system
What is meant by intercellular signalling?
Signalling between cells
What is meant by intracellular signalling?
Signalling within a cell
What are the four methods of signalling?
- Autocrine
- Endocrine
- Paracrine
- Communication between membrane attached proteins
What is meant by endocrine communication?
When the hormone travels in the blood vessel and acts on a distant target cell
How does glucagon act as an example of endocrine signalling?
Glucagon is released by the alpha cells of the Islets of Langerhans, and then transported in the blood to act on the liver
This stimulates gluconeogenesis and glycogenolysis
How does insulin provide an example of endocrine communication?
Insulin produced by the pancreas acts on muscle and adipose tissue
How does adrenaline provide an example of endocrine communication?
Produced by the adrenal glands and travels in the blood to act on many body systems like the lungs and trachea
What type of communication is shown in response to hypoglycaemia?
Endocrine
What types of communication is shown in response to hyperglycemia and why?
Paracrine – beta cells release insulin which inhibits glucagon secretion from adjacent alpha cells
Endocrine – reduces glycogenolysis and gluconeogenesis in liver
What is meant by paracrine communication?
When the hormone that is released acts on the adjacent cell
How does the pancreas show paracrine communication?
Insulin produced by the beta cells acts on the adjacent alpha cells inhibit glucagon production
Describe how nitric oxide acts in a paracrine manner
Nitric oxide is produced by endothelial cells in blood vessels and causes vasodilation
Describe how osteoclast activating factors work in a paracrine manner
They are produced by adjacent osteoblasts
What is meant by membrane attached protein comunication?
When plasma proteins in the membrane of two different cells interact
Describe an immunological example of membrane-attached protein communication
APC detects a bloodborne virus
APC digests the pathogen and expresses MHC II on surface
Circulating T cell interacts with MHC II via T cell receptors
Give 2 other examples of signalling between membrane attached proteins
HIV GP120 glycoprotein binds to CD4 receptors on T lymphocytes
Bacterial cell wall components bind toll-like receptors on haematopoietic cells
What is meant by autocrine communicaiton?
When a hormone acts on the same cell that produced it
How do T cells display autocrine forms of communication?
When T cells become activated they express IL-2 receptors and also release IL-2 which mediates cytokine release and binds to the receptor on the same cell
How does ACh display autocrine signalling?
ACh binds to presynaptic M2 muscarinic receptors
How do growth factors show autocrine communication?
Growth factors from tumour cells can bind to and act on tumour cells to cause mitogenesis
Describe how neurotransmission occurs?
- Acton potential arrives at the synapse due to an influx of sodium ions into the pre-synaptic bouton
- This triggers the opening of voltage gated calcium channels, allowing an influx of Ca2+ into the neurone
- Ca2+ binds to vesicles containing NT
- The NT vesicles then move to the cell membrane and are released into the synapse through exocytosis
- They then bind to receptors on the post-synaptic neurone
What are the four distinct categories of receptors which exist?
- Ligand gated ion channel receptors
- G protein coupled receptors
- Enzyme-linked receptors
- Intracellular receptors
How do ligand-gated ion channel (ionotrophic) receptors work?
Ligand binds to receptor protein
Conformational change in the protein opens a pore
This allows the flow of ions in or out of the cell
How is the direction of the movement of ions through ionotrophic receptors determined?
Through concentration gradients
What is an example of an ionotrophic receptor?
Acetylcholine binds to nicotinic ACh receptors on skeletal muscle resulting in muscle contraction
What is the ligand for NMDA receptors?
Glutamate
What is the ligand for GABA alpha receptors?
GABA
What are G-coupled receptors also known as and why?
7-transmembrane receptors as the channel protein crosses the membrane 7 times
In resting state what does the G protein complex consist of?
Alpha subunit, beta-gamma subunit, and an associated GDP molecule
Describe how G coupled receptors work?
- G protein complex binds to G coupled receptor which is embedded in the cell membrane
- The GDP is phosphorylated and swapped with GTP
- The G protein complex dissociates into alpha and beta-gamma subunits with alpha binding to a target protein
- GTP is dephosphorlyated to GDP, thus the alpha subunit dissociates from the target protein and binds beta-gamma again
What is stimulated to convert ATP to cAMP?
AC - adenyl cyclase
What is cAMP?
Cyclic adenosine monophosphate
What does cAMP activate?
Protein kinase A
Which G protein linked receptor activates adenylyl cyclase?
Gs protein linked receptor
Which G protein linked receptor inactivates adenylyl cyclase?
Gi protein linked receptor
What is an example of a G protein linked receptor which stimulates adenylyl cyclase?
Beta 1-adrenergic receptor
What is an example of a G protein linked receptor which inacitaves adenylyl cyclase?
M2 muscarinic receptor
What is the downstream effect of Gq protein linked receptors?
Activates AT-1 angiotensin receptor due to protein kinase C being activated
How do enzyme linked receptors work?
- Ligand binds and receptors cluster
- Enzymes phosphorylate the receptor, causing binding of signalling proteins to the receptor’s cytoplasmic domain
- The signalling proteins recruit other ones, generating a signal in the cell
- Signal terminates when phosphatase dephosphorylates the receptor
What enzyme is activated when insulin binds to the insulin receptor?
Tyrosine kinase
What enzyme is activated when ANP and BNP bind to the NPR1 receptor?
Guanylyl cyclase
What enzyme is activated when TGF beta binds to TGF B receptors?
Serine/threonine kinase
What is the physiological effect of serine/threonine kinase activation?
Apoptosis
What is the physiological effect of activation of tyrosine kinase?
Glucose uptake and lipid metabolism
What is the physiological effect of activation of guanylyl cyclase?
Vasodilation and reduction in blood pressure
Where are type 1 intracellular receptors located?
Within the cytosolic compartment
Where are type 2 intracellular receptors located?
In the nucleus
What chaperone molecules are type 1 intracellular receptors normally associated with?
Heat shock proteins
How do type 1 intracellular receptors work?
- Hormone enters through membrane
- Binds to receptor, heat shock protein dissociates
- 2 hormone bound receptors form a homodimer
- Homodimer translocates to the nucleus and binds to DNA
How do type 2 intracellular receptors work?
The hormone ligand binds straight to the DNA in the nucleus
What is an example of a type 1 intracellular receptor?
Glucocorticoid receptor
What ligands binds to the glucocorticoid receptor?
Cortisol and corticosterone
Physiological effect of cortisol binding to glucocorticoid receptor?
Reduced immune response and increased gluconeogenesis
What is an example of a type 2 intracellular receptor?
Thyroid hormone receptor
What is the associated ligand for the thyroid hormone receptor?
Thyroxine and triiodothyronine
With type II intracellular receptors, what causes the direct transcriptional regulation?
Activated hormone-receptor complex
What is a homodimer?
When two identical hormone receptor complexes join
Intracellular receptors are essentially what?
Transcription factors
Why do steroid hormones extert their actions on intracellular receptors?
They are membrane permeable
When the hormone binds to the receptor, what dissociates?
The heat shock protein
What is a ligand?
A molecule that binds to a receptor to exert a specific effect
