Week 10: Cell Signalling Flashcards

1
Q

How does signal transduction occur?

A

Membrane-bound receptors

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2
Q

What does binding of one ligand molecule lead to?

A

The production of many second messenger molecules

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3
Q

Why does receptors only remain active for a limited time?

A

Enables to see changes

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4
Q

When does de-sensitisation occur?

A

Continued exposure to the stimulus leads to a decreased response (the system responds most to changes in the level of a stimulus)

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5
Q

What is a second messenger?

A

Chemical signal produced in the cytoplasm

Go around and interact with things and changing the biochemistry of cells

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6
Q

Who won the chemistry Nobel Prize?

A

Robert Lefkowitz
Brian Kobilka
Focuses on G protein coupled receptors
Several proteins that reach through cell walls

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7
Q

What does Rhodopsin mediate?

A

Visual responses in the retina and receives light signals

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8
Q

What are the features of Rhodopsin?

A

Spans the membrane
Cytoplasmic side is conserved
Hydrophilic domains on the extracellular side

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9
Q

How does Rhodopsin work?

A

Retinal molecule - proton - flips its confirmation that starts pushing out the helices and make a conformational change a

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10
Q

What does Rhodopsin conversation light into?

A

Electrical signal

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11
Q

What is a special feature of a GPCR?

A

The signal inside the cell incomes a G protein because it binds GDP or GTP

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12
Q

What are the 3 protein subunits of G protein that are associated with GPCR?

A

Alpha, beta, gamma
Membrane associated
Peripheral membrane proteins

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13
Q

What is stage 1 of GPCR?

A

Ligand binds to the receptor
Protein domain is facing the outside world and induces conformational change of protein allowing things to happen on the other side of membrane
Structure of the domain will change - this change allows binding of a G protein complex to the cytoplasmic side of GPCR

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14
Q

What is stage 2 of GPCR?

A

Conformational change in the alpha unit in the G protein

All these proteins are somewhat flexible - structure of the alpha unit changes - causes the GDP to fall out

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15
Q

What happens in the activated state?

A

Bind less from GDP and more from GTP

GDP falls out and GTP binds instead

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16
Q

What is stage 3 of GPCR?

A

Once GTP is bound, the alpha subunit of the G protein loses interest in the receptor and in the G protein subunits

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17
Q

What do effectors have in common?

A

Sort of enzyme
Catalyse some sort of biochemical reaction by binding alpha subunit of the G protein
Catalyses the production of second messengers

18
Q

What are examples of second messengers?

A

Adenylyl cyclase

Cyclic AMP

19
Q

Adenylyl cyclase

A

Snips off two phosphates of the ATP
Reaction is energetically favourable
Needs a catalyst to make it happen

20
Q

Cyclic AMP

A

Hydrophilic molecule
Unique confirmation
Allows it to interact with other proteins in a specific way

21
Q

When is G protein only active?

A

As long as it binds to GTP

22
Q

What does G protein hydrolyse?

A

GTP to GDP

23
Q

What happens when GDP is bound?

A

Loses interest in its effector

Regains interest in its own beta and alpha subunits

24
Q

What is GRK?

A

A G protein coupled receptor kinase

25
Q

What does kinase do?

A

Takes phosphate and attaches to specific residues on cytoplasmic side of GPCR (phosphorylation)

26
Q

What does phosphorylation induce?

A

Binding of arrestin which binds to phosphorylated gdpcr

27
Q

What happens once arrestin is bound?

A

Don’t activate G protein

28
Q

What is the consequence of being exposed to some sort of stimulus?

A

More and more of the receptors for that stimulus will get inactivated

29
Q

What does phospholipids C perform?

A

Catalytic mechanism
Deplete PIP2
Generate inositol triphosphate (IP3h and diacylglycerol (DAG)

30
Q

What does phosphatidyl-inositol make?

A

GPI anchor

31
Q

What is phisphatidyl-inositol involved in?

A

Cell signalling processes

32
Q

What is phospholipase C involved in?

A

Signal transduction

33
Q

How does phospholipase C stuck to membrane surface?

A

Binding head group of inositol

34
Q

What does cell signalling system use?

A

Lipid and lipid breakdown products as second messengers

35
Q

What are phosphoglyceride subject to?

A

Attack by phospholipase

36
Q

What does phospholipase C (PLC) attack?

A

Bond between glycerol and phosphate

37
Q

What is PLC?

A

Effector activated by G-proteins

Found in plasma membrane

38
Q

What does PLC have?

A

PH domain
Bind to phosphoibositide e.g. PIP2
Causes breakdown of PIP2 - second messenger DAG, diacylglycerol and IP3

39
Q

Where does IP3 diffuse and what is it’s role?

A

Diffuses into cytoplasm and bind to receptors in SER

Trigger release of calcium

40
Q

What does DAG bind to?

A

Protein kinase - PKC activating it

41
Q

What does PLC mediate at number of tissues?

A
Mast cell = Histamine release 
Adrenal Medulla = Adrenaline release 
Pancreas = Insulin release 
Liver = glycogenosis, glycogen hydrolysis 
Adipose tissue = fat synthesis