Lecture 21/ 15 Flashcards
What are the three stages of cell signalling
1- reception
2- transduction
3- response
1- Reception
The target cell detects a signalling molecule that binds to a receptor at the cell surface
2 transduction
Reception of signal causes receptors to initiate a signal transduction pathways ( usually a series of steps )
Turn on or off proteins by phophorylation
3- response
The transduce signal triggers a specific response in the target cell
We learnt intracellular signalling can act as molecular switch in our general principles of cell signalling . How can intracellular signals be activated ?
These molecules are activated or inhibited by the addition or removal of phosphate group. This can occur in 3 ways
What are the three ways in which intracellular signalling molecules are phosphorylated?
1-phosphate group from an ATP molecule to the signalling molecule
Added by protein kinase
Removed by a protein phosphatase
Kinases and phosphatase target ion channels , transcription factors and other regulatory proteins
Phosphorylation cascades
2-phosphate grp added to a substrate using inorganic phosphate ( not from ATP)
ADDED by phosphorylase.
Phosphorylation cascades
3- G- protein (intracellular signalling molecule) swaps between GTP and GDP
GDP to GTP = GTP binding added P
GTP to GDP = GTP hydrolysis , removal of P , sped up by GAP
What are the three types of surface receptors
A- an ion channel coupled receptor
B- a G protein coupled receptor
C- an enzyme coupled receptor
An ion coupled receptor( transmitter gated ion channels)
Opens when an extracellular signal molecule binds to the receptor .
The extracellular signal is actually a chemical signaL and once it binds to an ion coupled receptor it is turned to an electrical signal
ions move through this gate which alters the membrane potential of the postsynaptic
Eg - neuromuscular junction - acetylcholine receptor , in which acetylcholine binds to the receptor for it to open
Common in- nerve and muscle cells
Acetylcholine receptor
It is a transmitter gated aqueous pore
Has 5 subunits from which 2 of them are similar
Acetylcholine binding site at the top
CLOSED CONFIRMATION OF THE RECEPTOR
- both sides of pores are negatively charged , this shows that when acetylcholine is bound to the receptor , positive charge ions like na and k can pas .
However, if the acetylcholine is not bound , the gate is closed and no ions can pass
OPEN CONFIRMATION
Acetylcholine is released by a motor neurone
Binds to BOTH side of the receptor ( on each similar 2 subunits)
receptor undergoes a conformational change
The hydrophobic tails moves apart, opening the gate
Na passes through it
Down its electrochemical gradient into the cytosol
Depolarizes the membrane
G protein coupled receptors stimulate a G protein
Major class of receptors
Has 2 binding sites- extracellular signalling molecule (binds outside) and G Protein ( binds inside)
Has 7 alpha helixes- multi-pass protein
Can also recognize small signal molecules (hormones) or proteins
Stimulation of G coupled receptor protein
INACTIVE STATE
both the receptor and g protein are inactive
ACTIVE STATE
an extracellular molecule binds to the receptor
Changes the conformation of the receptors
Which in turn changes the alpha conformation of the g protein
This change in alpha conformation allows g protein to exchange its GDP to GTP
The swap causes a second conformation change
The second conformation change activates alpha and beta gamma complex.
Beta gamma complex dissociate
Alpha interact with the target proteins , Or B can bind to another receptor and cause a cascade
The receptor remains active as long as the signal molecule is bond to it and therefore activates many G proteins
NOTE- alpha can activate 1 protein
Inactivation of G protein coupled receptor
When the extracellular molecule releases from the receptor
The alpha subunit hydrolyses and swaps GTP to GDP ( OCCURS WITHIN SECONDS OF PROTEIN ACTIVATION )
The hydrolysis of GTP inactivates the alpha subunit
That then assembles with BY complex
This assembly forms an Inactive G protein
Some G protein directly regulate ion channels . How?
This occurs in the plasma membrane of heart pacemaker cells for the opening of k+ channels in the plasma membrane
Acetylcholine binds to the GCPR on the heart cells
1st conformal change of receptor
2nd conformal change of g protein
Dissociation on ā and BY complex
BY complex attaches to the k channel in the plasma membrane
This opens the k channel
K goes out to the extracellular space
Result
Increases the permeability to k
Makes the membrane harder to activate
This slow the heart rate
To close the k channel ions
The ā unit hydrolysis and swaps from GTP to GDP ,INTURN ā gets dis active
Assembly of ā and BY complex
BY complex dis attach itself from the channel
Ion channel closes
The other G proteins activate membrane bound enzymes that produce small messenger molecules? Epinephrine
Extracellular molecular signal (epinephrine) activates receptor
Receptor activates g protein
This g protein affects adenylyl cyclase
Adenylyl cyclase increase the second messanger CAMP
The CAMP pathway :
- activates enzymes like protein kinase A (PKA]
The PKA:
- phosphorylates glycogen synthase, inactivating it.
- ATST PKA phosphorylates the enzyme phosphorylase kinase , activating it
The phosphorylase kinase :
- phosphorylates its target enzyme: glycogen phosphorylase, activating it
Glycogen phosphorylase:
- Phosphorylase catalyses glycogen breakdown
When does cAMP reaction occurs ?
when more glucose is needed and the glycogen needs to be broken down
Occurs in response to epinephrine
