Cell Signaling Flashcards
What are the four reasons we need cell signalling?
- To process information
- For self preservation
- For voluntary movement
- For 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?
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, to stimulate glyconeogenesis and glycogenolysis to make more glucose
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 type of communication is shown in response to hyperglycemia? and why
Paracrine and Endocrine - when blood glucose levels are too high, insulin is released which inhibits the secretion of glucagon from the alpha islet cells
Endocrine effects on the liver ie reduced glycogenolysis
What is meant by paracrine communication?
Hormone acts on an ADJACENT cell
How does the pancreas show paracrine communication?
Insulin produced by the Beta cells acts on the Alpha cells of the islet of langerhans to inhibit glucagon production
Describe how nitric oxide acts in a paracrine manner.
Nitric Oxide produced by the endothelium in blood vessels, acts on the smooth muscle to vasodilate the vessels
How do osteoclasts act in a paracrine manner?
Osteoclast activating factors produced by adjacent osteoblasts
What is meant by membrane attached protein comunication?
Plasma membrane proteins on adjacent cells interacting
Describe an immunological example of membrane-attached protein communication. (involving APCs)
1) Blood borne virus (e.g. hepatitis C) is detected within blood stream by antigen presenting cell (APC)
2) The antigen presenting cell (APC) digests the pathogen –> expresses major histo-compatibility (MHC) class II molecules on surface
3) Circulating T-lymphocytes engages with MHC molecule through T-cell receptor (TCR) interaction
How does HIV glycoproteins and bacterial cell wall components have “signalling between membrane attached proteins”?
→ HIV GP120 glycoprotein –> CD4 receptors on T-lymphocytes
→ Bacterial cell wall components –> toll-like receptors on haematopoietic cells
What is meant by autocrine communication?
Signalling molecules acts on same cell
How do T cells display autocrine forms of communication?
1) Activated TCR will initiate a cascade of reactions within T-cell
4) Activated T cell expresses interleukin-2 (IL-2) receptor on surface
3) 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
- Which mediates cytokine release
How does acetylcholine and growth factors act in an autocrine manner?
Acetylcholine –> presynaptic M2- muscarinic receptors
Growth factors (e.g. TGFbeta) from tumour cells (mitogenesis)
What are the overall types of signalling?
Endocrine: blood vessels-> distant target cell
Paracrine: hormone acts on adjacent cell
Membrane attached proteins: plasma membrane proteins on adjacent cells interacting
Autocrine: signalling molecule acts on same cell
Describe how neurotransmission occurs?
1) Propagation of the action potentials (AP)
- Action potentials are propagated by VGSCs (voltage gated sodium ion channels) opening
- Na+ influx –> membrane depolarisation –> AP ‘moves along’ neurone
- Voltage gated potassium ion channels opening –> K+ influx –> repolarisation
2) Neurotransmitter (NT) releases from vesicles
- Action potential opens voltage-gated Ca2+ channels at presynaptic terminal
- Ca2+ influx –> vesicle exocytosis
3) Activation of postsynaptic receptors
- Neurotransmitter binds to receptors on post-synaptic membrane
- Receptors modulate post-synaptic activity
4) Activation of postsynaptic receptors
- The signal can be transmitted by a variety of different types of receptor…
What are the four distinct categories of receptors which exist?
1) Ionotropic receptor
- Ligand binding –> opens ion permeable pore traversing the membrane
2) G protein coupled receptor
- Ligand binding –> activates intracellular G-protein
3) Enzyme-linked receptor
- Ligand binding –> receptor clustering –> activates internal enzymes
4) Intracellular receptor
A membrane permeable ligand binds to receptor inside cell
How do ionotrophic receptors work?
Signal transduction events…
1) Ligand binds to the receptor protein
2) Change in conformation of channel protein –> opening of a pore
3) Pore allows ions to move in or out of cell according to their respective concentration gradients
E.g.
- Nicotine acetylcholine
Ligand: acetylcholine (ACh)
Location: skeletal muscle
Physiological effect: muscle contraction
How is the direction of the movement of ions through ionotrophic receptors determined?
Through concentration gradients
What is an example of an ionotrophic receptor?
- Nicotine acetylcholine
Ligand: acetylcholine (ACh)
Location: skeletal muscle
Physiological effect: 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?
7-TRANSMEMBRANE RECEPTORS
In resting state what does the G protein complex consist of?
The Ga subunit, a GBγ subunit and an associated GDP molecule
Describe how G couples receptors work/ What are the signal transduction events?
1) 7-TM receptor and heterotrimeric G-protein are inactive
2) Ligand binding –> changes conformation of receptor
3) Unassociated G-protein binds to the receptor –> bound GDP molecule is phosphorylated to GTP
- GDP is exchanged for GTP
4) G-protein dissociates into 2 active components:
i. Alpha subunit
ii. Beta gamma subunit
–> bind to their target proteins
5) Internal GTPase activity on alpha subunit dephosphorylates GTP–> GDP
6) Alpha subunit dissociates from target protein –> inactive again
7) Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins
What is stimulated to convert ATP to cAMP?
AC - Adenylyl cyclase
What is cAMP?
Cyclic Adenosine monophosphate
What does cAMP activate?
Protein kinase A
Which g protein linked receptor activates adenylyl cyclase?
G s 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?
B1 - adrenergic receptor
What is an example of a G protein linked receptor which inacitaves adenylyl cyclase?
M2 - muscarinic receptor
What does the Gq protein linked receptor do?
Stimulates phospholipase C (PLC)
Give overviews of the 3 types of G protein linked receptors.
1. Gs protein linked receptor
Stimulates adenylyl cyclase
- Converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP)
- cAMP activates protein kinase A (PKA)
Example: b1-adrenergic receptor
2. Gi protein linked receptor
Inhibits adenylyl cyclase
- Reduces levels of PKA
Example: M2-muscarinic receptor
3. Gq protein linked receptor
Stimulates phospholipase C (PLC)
- Converts PIP2 to IP3 and DAG
- IP3 stimulates Ca2+ release
- DAG activates PKC
Example: AT-1 angiotensin receptor
How do enzyme linked receptors work?
- Ligand binds to receptor
- This results in receptor clustering
- The clustering activates enzyme activity within cytoplasmic domain
- The enzymes which are activated then phosphorylate the the receptor which leads to the binding of signalling proteins in the cytoplasmic domain
- These signalling proteins recruit other signalling proteins and a signal is generated within the cell.
- The signal is terminated when a phosphatase dephosphorylates the receptor.
What are the possible enzyme linked receptor pathwyas that can be activated?
PLC–> DAG–> PKC
Ras/ Raf/ Mek–> ERK1/2
JAK–> STAT
pAKT–> mTOR/ NFkb/ CREB
What enzyme is activated when insulin binds to the insulin receptor?
Tyrosine kinase
What enzyme is activated when ANP and BNP bind o the NPR1 receptor?
Guanylyl Cyclase
What is the ligand and physiological affect of the ErbB receptor?
Epidermal growth factor , transforming growth factor beta
Cell growth, proliferation
What enzyme is activated when TGR Beta binds to TGF B receptors?
Ser/Thr kinase
What is the physiological effect of Set/Thr 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/ cyotplasmic
Where are type 2 intracellular receptors located?
In the nucleus/ nuclear
How do type 1 intracellular receptors work?
Type 1- Cytoplasmic
1) Located within cytosolic compartment
2) Associated with chaperon molecules (heat shock proteins, hsp)
3) Hormone binds to receptor –> hsp dissociates
4) 2 hormone bound receptors form a homodimer
The homodimer translocates to the nucleus –> binds to DNA
How do type 2 intracellular receptors work?
Type 2- Nuclear
1) Located within the nucleus
Binding of hormone ligand –> transcriptional regulation
What chaperone molecules are type 1 intracellular receptors normally associated with?
hat shock proteins
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 and what is the physiological effect?
Thyroxine and triiodothyronine (T4 and T3)
Growth and development
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
