Cell Signalling Flashcards
Why do cells need to communicate? (4)
- Process information (from sensory stimuli)
- Self preservation eg. reflexes
- Voluntary movement
- Homeostasis
What are the 2 pathways of cell communication?
- Hormone
- Electrical impulses
What are the 4 different types of cell signalling?
- Endocrine
- Paracrine
- Membrane-attached protein
- Autocrine
What is endocrine signalling?
Hormone travels in blood to reach distant target cell
What is an example of endocrine signalling?
Hypoglycaemia glucagon action
How does hypoglycaemia control involve endocrine signalling? (3)
- Pancreas α-cells secrete glucagon
- Glucagon travels in blood
- Acts on liver —> glycogenolysis and gluconeogenesis
What is paracrine signalling?
Hormone acts on adjacent cell
What is an example of paracrine signalling?
Hyperglycaemia insulin action
How does hyperglycaemia control involve paracrine signalling? (2)
- β-cells detect increased blood glucose
- Insulin secreted —> acts on adjacent β-cells to inhibit glucagon secretion
What is membrane-attached protein signalling?
Interactions between plasma membrane proteins of different cells/particles
What is an example of membrane-attached protein signalling?
Cell-mediated response (APC and T-cell)
How does the cell-mediated immune response involve membrane-attached protein signalling?
- APC digests pathogen and expresses MHC II
- Th cell TCRs bind to MHC II
What is autocrine signalling?
Signalling molecule is acts on cell it comes from
What is an example of autocrine signalling?
T-cell IL-2
How does T-cell action involve autocrine signalling?
- Activated TCR initiates reaction cascade in T-cell
- Activated T-cell expresses IL-2 receptor on surface
- Activated T-cell secretes IL-2 —> binds to receptors on own cell
What are 3 steps of neurotransmission?
- Propagation on action potential
- VGSCs open —> Na+ influx —> action potential
- VGKCs open —> K+ influx —> repolarise - Neurotransmitter release
- Pre-s n VGCCs open —> Ca2+ influx —> vesicle exocytosis - Activation of post-s n
- Neurotransmitter diffuses across synapse —> binds to post-s n receptors
- Different types of receptors present
What are the 4 types of receptors post-s ns can have?
- Ionotropic
- G-protein coupled
- Enzyme-linked
- Intracellular
What is the main principle behind ionotropic receptors?
Ligand binds —> opens ion permeable pore across membrane
What is the main principle behind G-coupled protein receptors?
Ligand binds —> activates intracellular G-protein
What is the main principle behind enzyme-linked receptors?
Ligand binds —> receptor clustering —> activates internal enzymes
What is the main principle behind intracellular receptors?
Membrane permeable to ligand —> passes through
—> binds to intracellular receptor
What are the 3 steps in the mechanism of ionotropic receptors?
- Ligand binds to receptor
- Channel protein shape change —> opens pore
- Ions move in/out depending on gradient
What are are 2 examples of ionotropic receptors?
- Nicotinic ACh receptor
- GABA-A receptor
What type of receptors are nicotinic ACh receptors and what is their function?
Ionotropic
- Binds to ACh
- Stimulates muscle contraction
What are the 5 steps in the mechanism of G-protein coupled receptors?
- Ligand binds to GPCR
- GPCR changes conformation —> G-protein binds
- Stimulates GDP —> GTP (bound to Gα sub-unit)
- Stimulates G-protein dissociation —> Gα and Gβγ
- Gα and Gβγ bind to target protein
What are the 3 steps of the mechanism of GPCR deactivation?
- GTPase causes GTP —> GDP (bound to Gα sub-unit)
- Gα sub-unit dissociates from target —> inactive
- GPCR not deactivated till ligand isn’t bound
What is the shape of a GPCR?
Snakes crossing membrane 7 times (7-TM)
What is the quaternary structure of G-proteins?
Heterotrimeric —> α, β, γ
- α associated with GDP/GTP
- β and γ always together
What are the 3 types of G proteins?
- S
- I
- Q
What do Gs protein-linked receptors do?
Stimulate adenylyl cyclase:
-ATP —> cAMP —> PKA
What do Gi protein-linked receptors do?
Inhibit adenylyl cyclase
- less PKA
What do Gq protein-linked receptors do?
Stimulate phospholipase (PLC)
-PIP2 —> IP3 —> Ca2+ release
—> DAG —> PKC
What happens when Gs proteins stimulate adenylyl cyclase?
- ATP —> cAMP
- cAMP activates PKA (protein kinase A)
What happens when G proteins inhibit adenylyl cyclase?
Decrease protein kinase A (PKA) levels
What happens when Gq proteins stimulate phopholipase C?
- PIP2 —> IP3 + DAG
- IP3 stimulates Ca2+ release
DAG activates protein kinase C
What is an example of a Gs protein-linked receptor and what is its function?
β1-adrenergic receptor
- Adrenaline/NA binds —> inc heart rate
What is an example of a Gi protein-linked receptor and what is its function?
M2-muscarinic receptor
- ACh binds —> dec heart rate
What is an example of a Gq protein-linked receptor and what is its function?
AT-1 angiotensin receptor
- AT-1 binds —> vasoconstriction
- Hypertension drugs block AT-1 receptor
What are the 5 steps in the mechanism of enzyme-linked receptors?
- Ligand binds —> receptors cluster
- Activates enzyme activity in cytoplasmic domain
- Enzymes phosphorylate receptor via signal protein binding
- Starts signal protein cascade
Which type of receptor is involved in cell proliferation and why?
Enzyme-linked receptors
- Slowest
Which type of receptor can be a target for cancer drugs and why?
Enzyme-linked receptors
- involved in cell proliferation
How long does each type of receptor take to work?
- Ionotropic —> ms-s
- G-protein couples —> s-mins
- Enzyme-linked —> mins-hrs
- Intracellular —> hrs-days
Which type of receptor is the fastest?
Ionotropic
Which type of receptor is the slowest?
Intracellular
What are 2 examples of enzyme-linked receptors?
- Insulin receptor
- ErbB receptor
What are the 2 types of intracellular receptors?
- Type 1 —> cytoplasmic
- Type 2 —> nuclear
What are the 5 steps in the mechanism of type 1 intracellular receptors?
- Hormone passes across membrane
- Hormone binds to receptor in cytoplasm
- Hsp (heat shock protein) dissociates
- 2 Hormone-bound receptors join —> homodimer
- Homodimer to nucleus —> binds to DNA
What are the 2 steps in the mechanism of type 2 intracellular receptors?
- Hormone passes through membrane and cytoplasm
- Hormone binds to nuclear receptor —> regulates transcription
What is an example of a type 1 intracellular receptor?
Glucocorticoid receptor
What is an example of a type 2 intracellular receptor?
Thyroid hormone receptor
What are the ligands for and effects of glucocorticoid receptors?
- Ligands —> cortisol, corticosterone
- Effect —> dec immune response, inc gluconeogenesis
What are the ligands for and effects of thyroid hormone receptors?
- Ligands —> T3 (triiodothyronine), T4 (thyroxine)
- Effect —> growth, development
