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MCB > MCB8 - Cell Signalling > Flashcards

MCB8 - Cell Signalling Flashcards

1
Q

Give general overview of why cells need to communicate.

A

Vital for various physiological processes - homeostasis, visual processing, movement.

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2
Q

What is cell signalling and where do cells receive signals from.

A

Processing of information in form of input which is processed to give an output. Signals come from extracellular fluid, adjacent cells or extracellular matrix.

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3
Q

What happens in cells do not receive or interpret signals.

A

Commonly undergo cell death - apoptosis.

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4
Q

Give examples of inputs received by cells.

A

Environmental stresses, nutrient signals, extracellular matrix, internal stresses.

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5
Q

Give examples of cell outputs.

A

Gene expression changes. Senescence of cell. Growth or division. Morphological changes.

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6
Q

What are the five types of cell communication.

A 
Endocrine
Paracrine
Autocrine
Synaptic
Contact-dependent
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7
Q

Discuss endocrine cell communication with an example.

A

Uses hormones as signalling molecule which travel in the blood stream or circulation to distant target cell. Signalling cells are endocrine cells. Insulin produced in pancreas but acts in liver

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8
Q

Discuss paracrine cell communication with example.

A

Signalling molecule released into extracellular fluid therefore it acts locally on neighbouring cells. Histamines act locally on mast cells.

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9
Q

Discuss autocrine cell communication with example.

A

Signalling molecule acts on the same cell. Cytokine interleukin can act on same cell.

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10
Q

Discuss synaptic cell communication, with example.

A

Electrical transmission is propagated along a nerve axon. When axon terminal of Neuron is reached, neurotransmitter is released, to adjacent neuron across synaptic cleft. Electrical signal is converted into chemical one. Example - acetylcholine.

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11
Q

Give other name for contact dependent cell communication.

A

Juxtacrine signalling

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12
Q

Discuss contact dependent signalling with example.

A

Cells are in close proximity of one another and communication occurs directly via junctions in plasma membrane of cells. Example includes immune system where macrophage engulfs pathogen and displays antigen which is then detected by T cells.

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13
Q

Define signal transduction.

A

Conversion of signals from extracellular signalling molecule to intracellular signalling molecule and further downstream effects.

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14
Q

Define signalling and target cells.

A

Signalling cells produce extracellular signalling molecule. Target cells detects the signalling molecule.

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15
Q

What are the three ways information is transferred across the plasma membrane.

A

Passive diffusion
Gated channels
Transmembrane receptors

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16
Q

Discuss process of passive diffusion in cell signalling

A

Only for signalling molecules that are membrane permeable or lipid hormone small hormones. Passively diffuse across plasma membrane down concentration gradient. Causes change in cell behaviour once inside the cell.

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17
Q

Discuss use of gated channels in cell signalling.

A

Signalling molecule binds to ion channels causing a conformational change which opens the ion channel allowing ions through. Response is for specific signals.

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18
Q

Discuss use of transmembrane receptors in cell signalling.

A

Extracellular signalling molecule binds to transmembrane receptor protein with a ligand binding domain. Intracellular region of transmembrane receptor signalling effector proteins which eventually cause a change in cell behaviour.

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19
Q

How do transmembrane receptors in cell signalling ensure specific cell signals.

A

Each receptor is specific for a specific type of signalling molecule.

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20
Q

What are the two types of transmembrane receptors involved in cell signalling.

A

Cell surface receptors.

Intracellular receptors.

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21
Q

Discuss process by which cell surface receptors play a role in cell signalling.

A

Extracellular signalling molecule binds to extracellular region of transmembrane cell surface receptor. Intracellular/cytosolic region of transmembrane receptor protein. Information is passed on in form of intracellular signalling molecules.

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22
Q

Discuss process by which intracellular receptors play a role in cell signalling.

A

Small hydrophobic signalling molecules can pass through plasma membrane and interact with intracellular receptors.

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23
Q

Give three cells that acetylcholine acts on as an extracellular signalling molecule.

A

Heart pacemaker cells
Salivary gland cells.
Skeletal muscle cells.

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24
Q

Define a signalling cascade.

A

Series of events triggered by a signalling molecule binding to a receptor, with an overall result of a change in cell behaviour.

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25
Q

What are the three regions of a transmembrane receptor protein in the plasma membrane.

A

Extracellular region, transmembrane region, intracellular region.

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26
Q

What is the primary step of signal transduction.

A

The binding of an extracellular signalling molecule to the transmembrane receptor.

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27
Q

What do intracellular signalling proteins do as part of the signalling cascade.

A

Activate or generate the next downstream molecule

28
Q

What type of protein in a signalling cascade triggers a response from a cell..

A

Effector proteins.

29
Q

Give examples of cell responses as a result of signalling cascades.

A

Altered metabolism. Change in gene expression. Altered cell shape and movement

30
Q

Define the purpose of a scaffold protein.

A

Scaffold proteins hold multiple intracellular signalling molecules together leading to a faster activation rate of downstream effects or an amplification of downstream effects

31
Q

Discuss the amplification of a signal response.

A

Amplification of a single response introduces numerous small intracellular messenger molecules which make the response stronger and larger.

32
Q

Discuss the integration of a signalling cascade.

A

Integrating multiple signalling molecules into a signal response. Multiple signalling cascades can be combined into one pathway.

33
Q

Discuss distribution in a signalling cascade.

A

Signalling molecules are distributed to their effector protein or other signalling cascades allowing signal transduction to continue

34
Q

What are the two regulators of molecular switches

A

Regulation by G proteins (GTP binding proteins) or phosphorylation (protein kinase)

35
Q

What three amino acids become phosphorylated during protein phosphorylation for behaviour as a molecular switch. Which functional group do they contain.

A

Serine, threonine, tyrosine. OH functional group.

36
Q

Discuss process of protein phosphorylation in molecular switches.

A

Covalent addition of phosphate group at specific amino acid of protein, catalysed by protein kinases. Can lead to activation or inactivation. Phosphatase enzyme catalysed removal of phosphate group.

37
Q

Discuss use of G proteins as a molecular switch,

A

GTP binding proteins are activated when the bound GDP is exchanged for GTP. Upon activation, GTP is hydrolysed to GDP by internal GTPase activity. G protein is inactivated.

38
Q

What is the molecular switch function.

A

Regulatory component of signalling cascades.

39
Q

What are adaptor proteins

A

Regulatory component of signalling pathways. Acts as a bridge to bring two proteins closer together.

40
Q

Give example of adaptor protein and how it functions.

A

Adaptor protein Grb2 contains regions which interact with specific amino acids in proteins and so brings them together.

41
Q

What are the four types receptor classes of signal transmission

A

Ion channel linked receptor
G protein coupled receptor
Enzyme linked receptor
Intracellular receptor

42
Q

How are signals transmitted using ion channel linked receptors

A

Extracellular signalling molecule binds to receptor linked to ion channel. Conformational change occurs bringing about ‘open’ state. Ions can pass through ion channel, relaying signal

43
Q

How are signals transmitted using G protein coupled receptors. Give generalised overview.

A

Extracellular signalling molecule binds to outside of G protein coupled receptor. Results in activation of coupled G protein which has downstream effects.

44
Q

Discuss how signals are transmitted using enzyme linked receptors.

A

Extracellular signalling molecule binds to transmembrane receptor. Often the receptor dimerises which results in activation of intracellular enzyme.

45
Q

Discuss how signals are transmitted using intracellular receptors.

A

Only for extracellular signalling molecules that are plasma membrane permeable. Signalling molecule binds to intracellular receptor and causes change in cell behaviour. Commonly uses nuclear receptors which cause a change in gene expression.

46
Q

Give example of signalling molecule binding to intracellular receptor and its downstream effect.

A

Cortisol is steroid hormone so is membrane permeable. Binds to nuclear receptor protein. Cortisol-receptor complex moves into nucleus through nuclear pore. Binds to regulatory region of gene resulting in activation of transcription of that gene.

47
Q

What processes are involved in the movement of cortisol into nucleus, binding to nuclear receptor and its downstream effects.

A

Passive diffusion - cortisol is membrane permeable
Protein import into nucleus
Gene transcription - downstream effect

48
Q

Discuss role of ion channels in synaptic transmission.

A

Allows conversion of chemical signal into electrical signal. Chemical signal in form of neurotransmitter binds to ion channel linked receptor which opens ion channel allowing flow of ions. Results in change in membrane potential and so an electrical signal which can be propagated.

49
Q

Discuss general mechanism by which enzyme linked receptors aid cell signalling.

A

Primary signal transduction can be 1 of 2 options:
- extracellular signalling molecule in form of dimer binds to transmembrane receptor protein causing it to dimerise also.
-extracellular signalling molecule binds to inside of two transmembrane receptor, pulling them together into a dimer.
Enzyme continues cell signal in one of two ways:
-catalytic domain within transmembrane receptor protein becomes activated.
-associated enzyme becomes activated

50
Q

What processes are enzyme linked receptors commonly involved with

A

Growth, proliferation, differentiation and survival.

51
Q

Discuss link between anti cancer therapies and enzyme linked receptors

A

Enzyme linked receptors play major roles in cancer initiation and growth so targeting these can be useful for developing anti cancer therapies.

52
Q

What is the largest class of enzyme linked receptors

A

Receptor tyrosine kinases

53
Q

Discuss process by which receptor tyrosine kinase plays a role in cell signalling.

A

Dimerised Extracellular signalling molecule e.g. growth factors, bind to two receptors, causing them to dimerise. Kinase catalytic domain brought into close contact which activated them. Tyrosine residues becomes phosphorylated. Intracellular signalling proteins bind to phosphorylated tyrosine residues. Signal is relayed by activated signalling proteins.

54
Q

How are adaptor proteins involved in cell signalling by receptor tyrosine kinases.

A

Adaptor proteins bind to phosphorylated tyrosine residues on RTKs. This stimulates another signalling protein which relays the signal.

55
Q

What are Ras proteins and what activates them

A

Family of proteins with GTPase activity involved in onward signal transduction. Receptor tyrosine kinases activate Ras proteins

56
Q

How are Ras proteins activated and inactivated

A

Activation - GDP exchanged for GTP, promoted by guanine nucleotide exchange factors (GEFs)
Inactivation - GTP hydrolysed to GDP, stimulated by GTPase activating proteins

57
Q

How are Ras proteins involved in the onward transmission of a signal, after become activated.

A

Cause a protein kinase cAscade in form of MAP kinase case or ERK kinase cascade. These kinases have various effector protein targets which cause changes in protein activity and gene expression.

58
Q

Discuss link between Ras proteins and cancer.

A

A common mutation in cancer patients is mutation of Ras proteins. Results in stimulation of cells to divide even in absence of correct signal telling it to divide. Can result in cell proliferation of cancerous cells,

59
Q

What is a GPCR and discuss its physical structure,

A

G protein coupled receptors. Transmembrane proteins consisting of 7 transmembrane regions

60
Q

Discuss general overview of how GPCRs act in cell signalling. J

A

Extracellular signalling molecule binds to GPCR. Associated G protein becomes activated.

61
Q

What are the targets of G proteins and how long does the effects take to take place

A

Ion channels and membrane bound enzymes. Fast and reversible

62
Q

What are the three subunits of G proteins.

A

Alpha beta lambda

63
Q

Which subunit in a G protein binds the guanine nucleotide.

A

Alpha

64
Q

Discuss process by which heterotrimeric G proteins result in activation of their respective effector target.

A

Extracellular signalling molecule binds to GPCR. Associated G protein becomes activated by GTP binding to alpha subunit. After GTP binds, alpha subunit breaks off leaving beta+lambda subunit. Activated alpha subunit with GTP binds to target protein, resulting in change in cell behaviour. GTP hydrolysed to inactivate alpha subunit which then rebounds to beta+lambda subunit to form inactive G protein for re use.

65
Q

Describe the role of GPCRs in regulation of ion channels.

A

Extracellular signalling molecule binds to GPCR, activating coupled G protein. Beta+lambda activated subunit of G protein binds to closed ion channel, resulting in conformational change to open the ion channel. GTP hydrolysed to GDP in the alpha subunit which inactivated the beta+lambda subunit also. Inactivated subunits reform inactive G protein.

66
Q

Give example of regulation of ion channels by GPCRs

A

Acetylcholine binding to GPCR resulting in opening of K+ ion channel

67
Q

Discuss role of GPCRs in activation of membrane bound enzymes

A

Activated alpha subunit of G protein binds to enzyme that becomes activated. Enzyme commonly catalysed synthesis of intracellular signalling molecules e.g. second messengers. Signal becomes amplified.

MCB (13 decks)

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