Week 10: Cell Signalling Flashcards
How does signal transduction occur?
Membrane-bound receptors
What does binding of one ligand molecule lead to?
The production of many second messenger molecules
Why does receptors only remain active for a limited time?
Enables to see changes
When does de-sensitisation occur?
Continued exposure to the stimulus leads to a decreased response (the system responds most to changes in the level of a stimulus)
What is a second messenger?
Chemical signal produced in the cytoplasm
Go around and interact with things and changing the biochemistry of cells
Who won the chemistry Nobel Prize?
Robert Lefkowitz
Brian Kobilka
Focuses on G protein coupled receptors
Several proteins that reach through cell walls
What does Rhodopsin mediate?
Visual responses in the retina and receives light signals
What are the features of Rhodopsin?
Spans the membrane
Cytoplasmic side is conserved
Hydrophilic domains on the extracellular side
How does Rhodopsin work?
Retinal molecule - proton - flips its confirmation that starts pushing out the helices and make a conformational change a
What does Rhodopsin conversation light into?
Electrical signal
What is a special feature of a GPCR?
The signal inside the cell incomes a G protein because it binds GDP or GTP
What are the 3 protein subunits of G protein that are associated with GPCR?
Alpha, beta, gamma
Membrane associated
Peripheral membrane proteins
What is stage 1 of GPCR?
Ligand binds to the receptor
Protein domain is facing the outside world and induces conformational change of protein allowing things to happen on the other side of membrane
Structure of the domain will change - this change allows binding of a G protein complex to the cytoplasmic side of GPCR
What is stage 2 of GPCR?
Conformational change in the alpha unit in the G protein
All these proteins are somewhat flexible - structure of the alpha unit changes - causes the GDP to fall out
What happens in the activated state?
Bind less from GDP and more from GTP
GDP falls out and GTP binds instead
What is stage 3 of GPCR?
Once GTP is bound, the alpha subunit of the G protein loses interest in the receptor and in the G protein subunits
What do effectors have in common?
Sort of enzyme
Catalyse some sort of biochemical reaction by binding alpha subunit of the G protein
Catalyses the production of second messengers
What are examples of second messengers?
Adenylyl cyclase
Cyclic AMP
Adenylyl cyclase
Snips off two phosphates of the ATP
Reaction is energetically favourable
Needs a catalyst to make it happen
Cyclic AMP
Hydrophilic molecule
Unique confirmation
Allows it to interact with other proteins in a specific way
When is G protein only active?
As long as it binds to GTP
What does G protein hydrolyse?
GTP to GDP
What happens when GDP is bound?
Loses interest in its effector
Regains interest in its own beta and alpha subunits
What is GRK?
A G protein coupled receptor kinase
What does kinase do?
Takes phosphate and attaches to specific residues on cytoplasmic side of GPCR (phosphorylation)
What does phosphorylation induce?
Binding of arrestin which binds to phosphorylated gdpcr
What happens once arrestin is bound?
Don’t activate G protein
What is the consequence of being exposed to some sort of stimulus?
More and more of the receptors for that stimulus will get inactivated
What does phospholipids C perform?
Catalytic mechanism
Deplete PIP2
Generate inositol triphosphate (IP3h and diacylglycerol (DAG)
What does phosphatidyl-inositol make?
GPI anchor
What is phisphatidyl-inositol involved in?
Cell signalling processes
What is phospholipase C involved in?
Signal transduction
How does phospholipase C stuck to membrane surface?
Binding head group of inositol
What does cell signalling system use?
Lipid and lipid breakdown products as second messengers
What are phosphoglyceride subject to?
Attack by phospholipase
What does phospholipase C (PLC) attack?
Bond between glycerol and phosphate
What is PLC?
Effector activated by G-proteins
Found in plasma membrane
What does PLC have?
PH domain
Bind to phosphoibositide e.g. PIP2
Causes breakdown of PIP2 - second messenger DAG, diacylglycerol and IP3
Where does IP3 diffuse and what is it’s role?
Diffuses into cytoplasm and bind to receptors in SER
Trigger release of calcium
What does DAG bind to?
Protein kinase - PKC activating it
What does PLC mediate at number of tissues?
Mast cell = Histamine release Adrenal Medulla = Adrenaline release Pancreas = Insulin release Liver = glycogenosis, glycogen hydrolysis Adipose tissue = fat synthesis
