Cell signalling 2 Flashcards
What are the 3 main classes of cell surface signalling receptor?
> ion-channel-coupled receptors
G-protein-coupled receptors
Enzyme-coupled receptors
What do ion-channel-coupled receptors do?
Membrane depolarisation
What do G-protein-coupled receptors do?
Raise levels of second messenger molecules e.g. cAMP, Ca2+
What do enzyme-coupled receptors do?
Signals activate enzyme activity integral to the receptor
- activate own intrinsic enzymatic activity
What do changes in protein conformation allow?
Switching between active & inactive states in a reversible manner
How are proteins turned on & off via protein phosphorylation?
On: Protein kinase + ATP
(Adds Pi)
Off: Protein phosphatase
(Removes Pi)
How are proteins turned on & off via GTP-binding proteins?
On: GDP removed & GTP binds
Off: GTP hydrolysis
Removes Pi
What are the features of G protein coupled receptors (GPCR)?
> 7-pass transmembrane receptors
Have extracellular, transmembrane & intracellular domains
wide range of signals
Describe the structure of GPCR
3 subunits: alpha, beta & gamma
Alpha subunits = GTPase enzymes
= GTP -> GDP + Pi
What happens in the resting state of GPCR?
Trimeric G protein tethered to inner leaflet of plasma membrane
Alpha subunit associated w/ GDP molecule
Describe GPCR signalling
- Signal binds
- -> changes receptor conformation = allows G protein to bind to receptor - Alters G protein conformation
- -> promotes release of GDP = replaced by GTP - Further conformational change in alpha subunit
- -> activated & dissociates from beta & gamma complex & receptor
How is cardiac pacing regulated by the vagus nerve?
- AcH binds to receptor
- > GTP activates alpha subunit
- > leaves activated beta-gamma complex - activate beta-gamma causes K+ channel to open
= depolarises plasma membrane - G-protein inactivation via GTP hydrolysis removes Pi
- > alpha binds to beta-gamma complex
- -> K+ channel closes
How is GPCR signalling propagated by the active alpha/GTP subunit?
Alpha/GTP subunit associates w/ specific target enzymes
Target enzyme remains active while bound to subunit
= propagates the signal
How are GPCR signals self-inactivated?
Alpha subunit interacts with target enzyme
-> activates GTPase activity of subunit
-> subunit hydrolyses GTP to GDP
= restores inactive alpha subunit conformation
& causes release from target enzyme
= restores resting state (unless signal is still present)
What do enzymes activated by alpha/GTP subunits do?
Give examples
Raise the levels of second messenger molecules
Gs G proteins raise cAMP levels
Gq G proteins raise Ca2+ ion levels
Describe how alphaGs increases cAMP levels
- AlphaGs binds to adenylyl cyclase
2. Catalyses conversion of ATP -> cAMP via the removal of 2 Pi
How is cAMP signalling reversed?
cAMP broken down by a phosphodiesterase
= linear 5’-AMP
What do high levels of cAMP activate?
What does this result in the phosphorylation of?
A-kinase
cytoplasmic enzymes
–> changes their activity directly
TFs
–> alters gene expression
Describe how alphaGq increases Ca2+ levels
- Activated alpha subunit binds to Phospholipase C
- Converts Inositol phospholipid –> IP3
- IP3 binds to calcium ion channel
- Ion channel opens -> Ca2+ diffuses out of ER into cytoplasm
What do high levels of cytoplasmic Ca2+ cause?
Ca2+ binds to calmodulin
- > changes conformation
- > allows complex to interact w/ specific target proteins
- > alters target protein conformation + activity
Target proteins mainly = CaM-kinases (Ca2+/calmodulin modulated kinases)
