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Cell Biology (BY1CB1) > Week 6 (signalling & intracellular messengers) > Flashcards

Week 6 (signalling & intracellular messengers) Flashcards

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1
Q

Describe G protein coupled receptors

A
  • largest class of human cell surface receptors
  • involves in smell, taste, vision and hormone detection
  • bind a huge array of molecules
  • characterised by 7 transmembrane domains
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2
Q

GPCR activation

A
  • ligand binds to an extracellular site
  • changes to the conformation of the receptor
  • this recruits the G protein
  • at this point the G protein is inactive (GDP bound)
  • binding to the receptor induces GDP release; GDP is replaced by GTP
  • GTP bound G alplha separates from the GCPR and G beta gamma
  • Ga goes on to activate signalling cascades
  • An active GPCR can activate many G proteins.
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3
Q

Explain the properties of G proteins

A
  • G proteins act as molecular switches.
  • In the inactive state they are bound to GDP.
  • Activation of the G protein results in release of GDP.
  • This GDP is then replaced by GTP producing an active G protein.
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4
Q

G-proteins can activate Adenylyl-cylase: what is the function of adenylyl cylase?

A
  • Adenylyl-cyclase is a transmembrane protein
  • Adenylyl-cyclase can form cyclic AMP (cAMP) from ATP
  • cAMP is a potent SECOND MESSENGER
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5
Q

What are second messengers?

A

A diverse family of low molecular weight compounds such as cyclic AMP and calcium ions, which transmit the biological signals initiated by receptor-ligand binding at the cell surface to intracellular targets such as gene expression.

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6
Q

Give some examples of second messengers

A 
Second messengers – alter metabolism or affect effector enzymes that modulate target proteins and eventually cell behaviour.
Include:
cAMP
Ca2+
IP3
DAG
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7
Q

What are the G protein families?

A

4 families based on sequence homology.

Gs – stimulates adenylate cyclase.
Gi/o – inhibits adenylate cyclase.

Gq/11 – stimulates PLCB (phospholipase C beta).
G12/13 – activates RhoGEFs.

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8
Q

What are the cellular effects of cAMP?

A
  • Activation of cAMP-dependent protein kinase A (PKA)

- Protein kinase A can phosphorylate multiple targets

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9
Q

What are some cellular effects of Ca2+?

A
  • Activates calmodulin (calcium binding proteins)
  • Activates together with Calmodulin Ca2+/calmodulin dependent kinases (CaM-kinases)
  • Modulates the activity of loads of other proteins
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10
Q

How can G-proteins control channel opening?

A

Indirectly (via cAMP, IP3 and Ca2+ or phosphorylation by PKA, PKC, CaM-kinase)

Directly by binding to the channels and modulating their activity

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11
Q

what are Downstream events of gated

channel signalling?

A

opening of channels leads to ion fluxes across the membrane
as a result the membrane potential is changed (hyperpolarisation or depolarisation)
intracellular ion concentrations rise
(Most importantly: Ca2+)

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12
Q

What is the function of receptor signalling cascades?

A

Can detect a single molecule of ligand e.g. a photon.
Transduce this signal across the membrane.
Rapidly amplify this signal.
Activate a cascade of proteins that bring about appropriate cell behaviours.

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13
Q

What are the 3 subunits of G proteins

A

Alpha (Bound to GDP)
Beta
Gamma

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14
Q

What can Gq proteins do?

A

They can activate phospholipids C (PLC beta)

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15
Q

What are the the 4 subunits of protein kinase A?

A

It is a tetromer:
2 regulatory subunits
2 catalytic subunits

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16
Q

How many units of cAMP can bind to protein kinase A?

A

4

17
Q

What happens after cAMP bind to protein kinase A?

A

Regulatory subunits dissociate from catalytic subunits which become active

18
Q

What is the function of phospholipase C?

A

It cleaves (hydrolyses) phospholipids

19
Q

Describe the prices by which Gq proteins activate phosholipase C

A
  • signal molecule binds to GPCR
  • Gq protein recruited
  • Gq protein exchanges GDP for GTP and becomes active
  • the alpha subunit activates phosphlipase C
  • phosplipase C cleaves the inner leaflet of the membrane (phosphoinositde 4,5- bisphosphate )
  • phospholipase cleaves part of that molecule leaving part of it (diacylglycerol) attached to the inner leaflet of the membrane
  • produces IP3
20
Q

What are the consequences of phospholipase C activation?

A
  • IP3 is the ligand for gated Ca2+ channels

- binding causes the release of Ca2+ (second messenger)

21
Q

What two secondary messengers activate protein kinase C?

A

Diacylglycerol and Ca2+

22
Q

Explain the receptor signalling cascades involved in vision:

A
  • one rhodopsin molecule absorbs one photon
  • G protein molecules are activated
  • cGMP phosphodiesterase molecules are activated
  • cGMP are hydrolysed
  • Na+ channels close
  • Na+ prevented from entering the membrane
  • hyperpolarisation occurs
23
Q

G proteins as molecular switchses: what acts as the GEFs (Guanine nuclrotide exchange factors)?

A

GPCRs

24
Q

How can protein kinase A modulate transcription?

A

-Protein kinase A can modulate transcription (gene expression) by phosphorylating transcription factors

25
Q

How many subunits does protein kinase A have?

A

4 subunits

2 Regulatory +2 catalytic

26
Q

How many cAMP molecules can bind to cAMP dependant protein kinase A?

A

4

27
Q

What happens when 4 cAMP molecules bind to the 2 Regulatory subunits of cAMP dependent protrin kinase A?

A
  1. The catalytic subunits will dissociate from the regulatory subunit.
  2. Catalytic subunits are not active so can phosphorylate target proteins with serine or threonine residues
28
Q

What happens when 4 cAMP molecules bind to the 2 Regulatory subunits of cAMP dependent protrin kinase A?

A
  1. The catalytic subunits will dissociate from the regulatory subunit.
  2. Catalytic subunits are now active so can phosphorylate target proteins with serine or threonine residues
29
Q

Why is cAMP short lived?

A

The enzyme cyclic AMP phosphodieterase converts cAMP to (5’) AMP

30
Q

What happens when phospholipase C is activated?

A

It cleaves a component of the inner leaflet- phosphoinositide 4,5 bisphosphate

  • diacyl glycerol stays attached to the inner leaflet
  • inositol 1,4,5 triphosphate (IP3) is released
31
Q

What is the function of diacylglycerol?

A

Activates protein kinase C

32
Q

What is the function of IP3?

A

Releases Ca 2+ from ER

33
Q

What 2 second messengers activate protein kinase C?

A

Diacylglycerol

Ca2+

34
Q

What is a calmodulin?

A

A calcium binding protein

35
Q

What are CaM-kinases?

A

Calmodulin dependent kinases

36
Q

What activates phosphodiesterase?

A

A G protein

Cell Biology (BY1CB1) (16 decks)

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