Intro To Cell Signalling

Question 1

Why is cell signalling needed?

Answer 1

Question 2

What’s the effect of a cell receiving a signal

Answer 2

Apoptosis
Bring material into the cell
Divide
Differentiate
Express a gene

Question 3

What is the general process of cell signalling

Answer 3

1. Signal binds to receptor on the plasma membrane
2. Receptor will then change shape
3. Triggers a cascade of intracellular signalling proteins to effector proteins
4. Effector proteins carry out a response e.g altered metabolism, altered gene expression, altered cell shape or movement

Question 4

What is positive feedback and how does this happen

Answer 4

Response becomes stronger/ increases
The cell may do this by increasing the number of receptors

Question 5

What are the different types of cell signals

Answer 5

Question 6

What are the characteristics of cell signals

Answer 6

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

Question 7

How do signals bind to receptors

Answer 7

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)

Question 8

How do intracellular receptors bind to a hydrophobic signal

Answer 8

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

Question 9

What are the steps in many signalling pathways

Answer 9

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

Question 10

What is the role of a scaffold protein in cell signalling

Answer 10

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

Question 11

Name the 3 major types of receptors on the cell surface

Answer 11

Ion channel coupled receptors
G protein couplesd receptors
Enzyme coupled receptors

Question 12

How do ion channel coupled receptors work

Answer 12

Ligand binds to receptor causing the channel to open or close

change ion permeability of membrane (temporarily) e.g in nerve cells

Question 13

How do G protein coupled receptors work

Answer 13

Receptor activated -> activated G protein
Triggers downstream signalling

indirectly regulate activity of separate plasma-membrane bound target protein(either an enzyme or ion channel)

Question 14

How do enzyme coupled receptors work

Answer 14

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

Question 15

How can cells adjust their sensitivity to extra cellular signals

Answer 15

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

Question 16

What are some examples of small hydrophobic ligands

Answer 16

Steroids, thyroid, retinoids, vit D, some intracellular metabolites such as lipid products
Extracellular signal molecule= ligand

Question 17

How do receptors that act in the nucleus work

Answer 17

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

Question 18

What is meant by a molecular switch

Answer 18

on receipt of a signal they switch from an inactive to an active state, until another process switches them off

Question 19

What are the two classes of intracellular olecular switches

Answer 19

Both involve gain and loss of phosphate groups
1. Phosphorylation via kinases and phosphatases
2. Gtp- binding proteins

Question 20

What is the role of kinases

Answer 20

They’re a group of enzymes that adds phosphate groups to molecules

Question 21

What is the role of phosphatases

Answer 21

Enzymes that removes phosphate groups from molecules

Question 22

How does phosphorylation dependent signalling switches work

Answer 22

kinase adds phosphate from ATP to signalling protein (activates) phosphatases removes the phosphate- inactivates signal protein

Question 23

How do GTP-binding proteins work

Answer 23

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

Question 24

What are guanine exchange factors (GEFs)

Answer 24

Proteins that switch on GTP binding proteins by catalysing the binding of GTP to them

Question 25

What is the role of intracellular signalling proteins

Answer 25

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

Question 26

What is contact dependent signalling

Answer 26

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)

Question 27

What is a signal tranducer

Answer 27

signal transducers- convert an extracellular ligand binding event into intracellular signals that change the behaviour of the target cell

Question 28

What is the role of a trimeric GTP binding protein

Answer 28

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)

Question 29

What do large trimeric Gtp binding proteins do

Answer 29

Relay signals from G proteins coupled receptors

Question 30

What do monomeric gtpases do

Answer 30

Relay signals from cell surface receptors

Question 31

How can the coordination of multiple responses occur

Answer 31

• 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

Question 32

What is signal integration

Answer 32

• 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

Question 33

What do GPCRs do

Answer 33

Use G proteins to relay signals into the cell

Question 34

What happens when a signal binds to a GPCR

Answer 34

• 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

Question 35

How do GCPRs work

Answer 35

• 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

Question 36

How is a GPCR inactivated

Answer 36

• 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)