L12: Cell Signalling Flashcards
What does multicellular cells require for correct functioning of the organism?
Communication
Scientific term for communication between cells
Intercellular communication
Why do cells need to communicate?
- To Grow
- To divide
- To differentiate
- To move
- To secrete
- To die
- To store energy
What do all the processes require in order to proceed?
Signals
4 modes of intercellular communication
1) Endocrine
2) Paracrine
3) Neuronal
4) Contact-dependent
Where does endocrine signalling occur?
Whole body
What does endocrine signalling involve?
Involves the release of signaling molecules into the bloodstream.
These molecules are then transported to distant target cells- they bind to specific receptors and elicit a response.
What is the name of a cell-to-cell signalling mechanism that relies on the transport of signalling molecules via the bloodstream?
Endocrine
Where does paracrine signalling occur?
Within tissue
How does paracrine signalling operate?
Involves signaling molecules acting on nearby cells, typically within a localized area, and does not involve the bloodstream.
Define autocrine signalling
Signalling cell releases local mediator, however itself has a receptor
How does neuronal signalling operate?
1) Action potential moves down the presynaptic neurone, causing a change
2) Release of neurotransmitters diffuse across synaptic cleft, then bind to receptors on the postsynaptic cell
What is contact-dependent signalling for?
Cell Adhesion
How does contact-dependent signalling operate?
nvolves direct interaction between cells through membrane-bound signaling molecules and receptors, without transport through the bloodstream. that binds to the receptor on the target cell
4 examples of signalling factors
1) Hormones
2) Growth factors
3) Neurotransmitters
4) Metabolic regulators
True or False: Signalling molecules tend to be hydrophobic
FALSE
Hydrophilic
What 2 factors are important in ligand receptor binding?
1) High selectivity
2) High affinity
How does cell-surface receptors operate?
1) Cell surface receptor embedded in plasma membrane of target cell
2) Hydrophilic signal molecule binds to the cell surface membrane
How does intercellular receptors operate?
1) Small hydrophobic signal molecule diffuse across plasma membrane
2) In cytoplasm, it binds to receptors in the cytoplasm
3) Whole receptor signalling complex moves into the nucleus
3 major membrane receptor families
1) Ion channels
2) G protein-coupled receptors
3) Enzymes
2 types of ion channel-coupled receptors
1) Voltage gated
2) Neurotransmitter gated
How is the voltage gated receptors regulated by?
Changes in membrane potential
How is the neurotransmitter receptors operate?
Signal molecule bind to ion channel, which causes ion channels to open and ions flood in
What is another name given to G protein-coupled receptors?
7 pass transmembrane receptors
They pass through the membrane 7 times
Define heterotrimer
made up of 3 different subunits
Name the 3 different subunits in GPCR signalling
1) alpha
2) beta
3) gamma
Where are the subunits present?
Inner leaflet of the plasma membrane
What happens when the signalling molecule binds to G protein-coupled receptor?
G protein coupled receptor undergoes conformational change where the 3 subunits become associated with it
What does this conformational change cause to the a-subunit?
Exchange GDP for GTP
What happens to the a-subunit once it is bounded to GTP?
Dissociates away from beta & gamma subunit
What does a-subunit associate with as it moves along the inner leaflet of the plasma membrane?
Enzyme: adenylyl cyclase
What does this binding of a-subunit & adenylyl cyclase cause?
Conversion of ATP into cyclic AMP
What is activated when ATP is converted to cAMP “
Adenylcyclase
What bond converts cAMP to AMP ?
Cyclic AMP phosphodiesterase
What does it mean when protein kinase A is a heterodimer?
2 subunits that are structurally & functionally different
How does cAMP act as a 2nd messenger?
1) Increasing levels of cAMP activates protein kinase A
2) Causes cAMP to bind to regulatory subunit which moves away from the catalytic subunit that it is bound to
3) Catalytic subunit then phosphorylates proteins on serine & theorenine amino acids
Function of protein kinase A
phosphorylates proteins & activates them
Function of protein phosphatase & why it is important?
Remove phosphate groups, important as proteins shouldn’t be active all the time
How does protein kinase A execute signalling?
Protein kinase uses phosphate from ATP, phosphorylates protein & activates it
GPCR signalling at the membrane
Describe the stimulation of adenylyl cyclase
Include:
- Signalling molecule
- a, b, g subunit
- GDP/GTP
- Adenylyl cylclase
- ATP & cAMP
- Signalling molecule binds to G protein-coupled receptor
- G protein-coupled receptor undergoes conformational change where alpha, beta & gamma subunits are associated with it
- Changes cause a-subunit to exchange GDP for GTP
- When GTP is bound to a-subunit, it dissociates away from beta & gamma subunit
- a-subunit moves along the inner leaflet of plasma membrane & associates with enzyme adenylyl cyclase
- Which converts ATP into cAMP
How does cell signallling work in adrenaline in muscles ?
1) Adrenaline binds to GPCR, its receptors undergo change and associates it with a-subunit of G protein, which causes it to exchange GDP to GTP
2) a-subunit detaches from beta & gamma subunits and move along the membrane to activate adenylyl cyclase
3) Adenylyl cyclase converts ATP into cAMP
4) PKA phosphorylates glycogen synthase which inhibits glycogen synthesis
5) And PKA phosphorylates glycogen phosphorylase which stimulates it to increase glycogen degradation
Define glycogen degradation
Glycogen to glucose
Describe the activation of protein kinase C
1) Signalling molecule binds to G protein to activate a-subunit which activates phospholipase C
2) Phopholipase C breaks down inositol phospholipids into diacylglycerol which releases IP3
3) IP3 binds to Ca2+ channels in endoplasmic reticulum and causing channels to open, Ca2+ diffuses out
Beta - adrenergic
Give the:
- G protein
- Effector enzyme
- 2nd messenger
- Effect
- Gs
- Adenylyl cyclase
- cAMP
- Gluconeogenesis (non-carbs to glucose)
alpha1 - adrenergic
Give the:
- G protein
- Effector enzyme
- 2nd messenger
- Effect
- Gq
- Phospholipase C
- IP3, Ca2+
- Smooth muscle contraction (vasoconstriction)
What does b-ARs activate?
Adenylyl cyclase
What does a2-ARs activate?
a-subunit of G protein
What does a1-ARs activate?
GQ a-subunit
Describe receptor tyrosine kinase pathways
1) ECF binds to receptor, activates change & activates RAS
2) RAS phosphorylates EGF receptor to change GDP to GTP, RAS is absorbed
3) RAS associates with another kinase to phosphorylate RAF
4) RSF phosphorylates MEK1/2
5) MEK1/2 phosphorylates ERK1/2
6) ERK moves into nucleus to regulate transcription which leads to cell proliferation
