Intro To Cell Signalling Flashcards
Why is cell signalling needed?
What’s the effect of a cell receiving a signal
Apoptosis
Bring material into the cell
Divide
Differentiate
Express a gene
What is the general process of cell signalling
- Signal binds to receptor on the plasma membrane
- Receptor will then change shape
- Triggers a cascade of intracellular signalling proteins to effector proteins
- Effector proteins carry out a response e.g altered metabolism, altered gene expression, altered cell shape or movement
What is positive feedback and how does this happen
Response becomes stronger/ increases
The cell may do this by increasing the number of receptors
What are the different types of cell signals
What are the characteristics of cell signals
Signals act over different distances and time e.g may act on cells far away (only act on cells with specific receptors)
Cell response depends on the context e.g neurotransmitters act in milliseconds
Different cells can’t respond in different ways to the same signal
How do signals bind to receptors
Receptors bind to low concentrations of signal (<10^-7M) with high affinity (non covalent interactions)
On cell surface ligand binds and induces conformation change (hydrophilic receptor binds to hydrophilic signal)
Or inside they cell- diffusion through the plasma membrane (intracelular receptors bind to a hydrophobic signal)
How do intracellular receptors bind to a hydrophobic signal
Hydrophilic signal molecules are unable to cross plasma membrane which is why they bind to receptors
Some signal molecules (hydrophobic) diffuse across plasma membrane and bind to receptors inside the cell via carrier proteins -> they dissociate from the carrier protein before entering the cell
What are the steps in many signalling pathways
Signal binds to receptor
Primary transduction
Relay
Transducer and amplify (amplify response - will affect many proteins)
Integrate - converge signals from different pathways
Spread
Anchor (with anchor protein)
Modulate (regulate strength of signalling pathway)
Effector protein activation
What is the role of a scaffold protein in cell signalling
Scaffold proteins bring together groups of interacting signalling proteins into signalling complexes
It holds the proteins close together so they can interact at high concentrations and be activated quickly
Also avoids unwatnted cross-talk with other signalling pathways
Name the 3 major types of receptors on the cell surface
Ion channel coupled receptors
G protein couplesd receptors
Enzyme coupled receptors
How do ion channel coupled receptors work
Ligand binds to receptor causing the channel to open or close
change ion permeability of membrane (temporarily) e.g in nerve cells
How do G protein coupled receptors work
Receptor activated -> activated G protein
Triggers downstream signalling
indirectly regulate activity of separate plasma-membrane bound target protein(either an enzyme or ion channel)
How do enzyme coupled receptors work
Subunits of receptor floating around inactive plasma membrane
When the ligand binds it pulls the 2 subunits together (forms a dimer)
The ligand binds to active catalytic domain
usually single pass transmembrane proteins + have ligand binding site outside the cell and active site inside the cell
They either function as an enzyme of are directly associated with the enzymes that they activate
How can cells adjust their sensitivity to extra cellular signals
Receptor sequestration -> receptor hidden in endosome to prevent signalling
Receptor down regulation -> destruction of receptors in lysosomes (signal induced receptor endocytosis)
Receptor inactivation -> by phosphorylating the receptor
Inactivation of signalling protein
Production of inhibitory protein- blocks signal transduction
What are some examples of small hydrophobic ligands
Steroids, thyroid, retinoids, vit D, some intracellular metabolites such as lipid products
Extracellular signal molecule= ligand
How do receptors that act in the nucleus work
The ligands that bind to receptors in the nucleus are hydrophobic
Ligands bind to intracellular receptors either in cytosol and then move into nucleus or when bound to DNA regulatory regions
(Receptor forms e.g receptor-hormone complex which binds to sites on chromatin, activating mRNA transcription)
Can alter gene transcriptions
What is meant by a molecular switch
on receipt of a signal they switch from an inactive to an active state, until another process switches them off
What are the two classes of intracellular olecular switches
Both involve gain and loss of phosphate groups
1. Phosphorylation via kinases and phosphatases
2. Gtp- binding proteins
What is the role of kinases
They’re a group of enzymes that adds phosphate groups to molecules
What is the role of phosphatases
Enzymes that removes phosphate groups from molecules
How does phosphorylation dependent signalling switches work
kinase adds phosphate from ATP to signalling protein (activates) phosphatases removes the phosphate- inactivates signal protein
How do GTP-binding proteins work
is induced to exchange bound GDP to GTP -> activates protein
Protein deactivates by hydrolysing its bound GTP to GDP
Gtpase activating proteins switch off Gtp binding proteins by increasing rate of hydrolysis of the Gtp bound to it
guanine exchange factors activate the protein by stimulating it to release its GDP since conc. of GTP is high in cytosol
What are guanine exchange factors (GEFs)
Proteins that switch on GTP binding proteins by catalysing the binding of GTP to them
What is the role of intracellular signalling proteins
intracellular signalling proteins process the signal inside receiving cell and distribute it to intracellular targets (effector proteins) by generating second messengers or activating next signalling or effector protein in the pathway
(They act as molecular switches)
switch from inactive to active state until another process switches them off
What is contact dependent signalling
extra cellular signal molecules remain bound to the surface of the signalling cell and only influence the cells that contact it (require cells to be in direct membrane-membrane contact)
What is a signal tranducer
signal transducers- convert an extracellular ligand binding event into intracellular signals that change the behaviour of the target cell
What is the role of a trimeric GTP binding protein
trimeric GTP binding protein brings about the interaction between activated receptor and target protein (the enzyme or ion channel)
The target protein can chance conc of intracellular signalling proteins (if its an enzyme) or change ion permeability (if its an ion channel)
What do large trimeric Gtp binding proteins do
Relay signals from G proteins coupled receptors
What do monomeric gtpases do
Relay signals from cell surface receptors
How can the coordination of multiple responses occur
• coordination of multiple responses can occur through a single extracellular signal
• This depends on mechanisms for distributing a signal to multiple effects by creating branches in the signalling pathway
What is signal integration
• multiple extracellular signals may be needed for more complex cell behaviours
• The cell has to integrate info from multiple signals (which is done by intracellular coincidence detectors - these are proteins)
• These proteins are only activated if they receive multiple converting signals
What do GPCRs do
Use G proteins to relay signals into the cell
What happens when a signal binds to a GPCR
• when extracellular signal molecule binds to a GPCR -> receptor undergoes conformational change -> it then activates trimeric GTP binding protein (G protein)
• The G protein links the receptor to enzymes or ion channels
How do GCPRs work
• G proteins have three subunits: alpha, beta and gamma
• Unstimulated state- alpha subunit is bound to GDP and G protein is inactive
• when GPCR is activated it acts as a guanine exchange factor - it induces alpha subunit to release GDP, allowing GTP to bind in its place
• This then causes the G protein to be released from the receptor which causes the alpha subunit to dissociate from the beta-gamma pair
• The beta-gamma pair then interact with targets e.f enzymes/ ion channels in the plasma membrane with relay the signal onwards
How is a GPCR inactivated
• the alpha subunit becomes inactive when it hydrolyses s bound GTP to GDP
• (GTPase aka GTP binding protein- enzymes that hydrolyse GTP to GTP - removes phosphate)
