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PCS Unit 3 - Communication and Control > Week 9 - Cell Signalling > Flashcards

Week 9 - Cell Signalling Flashcards

1
Q

What is paracrine signalling?

A

released signal affects cells in close proximity

limited travel ability

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2
Q

What is autocrine signalling?

A

sender and target cell the same

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3
Q

What is endocrine signalling?

A

hormone secretion into the blood, acts on distant target cells

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4
Q

What is juxtacrine signalling?

A

the signalling cell is in direct contact with the target cell

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5
Q

Where are receptors located on cells?

A

in the plasma membrane (cell surface receptors)

inside the cell (within the cytoplasm or nucleus)

plasma membrane - responds to polar molecules

inside the cell - responds to non-polar molecules

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6
Q

What are the different classes of membrane receptor?

A

ion channel-linked receptors

G protein-coupled receptors

enzyme-linked receptors

nuclear receptors

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7
Q

What is an allosteric binding site?

A

the site the effector molecule binds to

in an ion channel-linked receptor this is where the ligand binding location is

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8
Q

What is another name for ion channel-linked receptors?

A

ionotropic receptos

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9
Q

What is another name for G protein-coupled receptors?

A

metatropic receptors

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10
Q

What are the three types of extracellular signal?

A

hormones

cytokines

growth factors

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11
Q

How to G protein-coupled receptors (GPCR) work?

A

ligand binds to GPCR causing a conformational change

G protein can now bind (GDP is exchanged for GTP)

alpha subunit dissociates

more intracellular signalling proteins activated

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12
Q

What G-protein subunit is activated when the protein binds to a GPCR?

A

alpha sub-unit

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13
Q

Describe the cAMP dependant pathway

A

1) GPCR activated by extracellular ligand
2) conformational change induced in receptor
3) Gs alpha subunit is exchanges GDP for GTP and is released from the complex
4) activated Gs alpha sub-unit binds to adenylyl cyclase
5) adenyl cyclase catalyses the conversion of ATP into cAMP
6) increase in concentration of cAMP activated PKA

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14
Q

Give examples of some second messengers

A

cAMP

cGMP

diacylglycerol (DAG)

inositol triphosphate (IP3)

phosphotidylinositol triphosphate (PIP3)

Ca2+

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15
Q

Give examples of ligands that act through GPCR’s?

A

serotonin, acetylcholine, epinephrine (adrenalin), glucagon and prostaglandins

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16
Q

Describe how an enzyme-linked receptor works?

A

ligand binding usually induces receptor to dimerise

this activates connected enzyme

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17
Q

What G protein alpha sub-unit switches on adenylyl cyclase?

A

Gs

s = stimulatory

18
Q

How is the cAMP signal terminated in the cell?

A

cyclic AMP phosphodiesterase converts cAMP to AMP

caffeine can inhibit this enzyme which keeps cAMP high, therefore acting as a stimulant

19
Q

How does cAMP activate PKA?

A

cAMP binds to the regulatory subunits causing the catalytic subunits to dissociate

20
Q

How does Ca2+ act as an intracellular second messenger?

A

moved around in the cytosol which varies the concentration and initiates the signal

Ca2+ levels can increase by release of calcium from intracellular stores (ER/mitochondria) or influx of Ca2+ from outside cell

21
Q

What is calmodulin?

A

calcium ion binding protein

is activated at high concentrations of calcium and binds to proteins and enzymes that calcium cannot bind to itself

22
Q

True or False:

calmodulin regulates the intracellular Ca2+ concentration

A

False

calmodulin senses but does not regulate intracellular calcium concentration

23
Q

How are DAG and IP3 produced?

A

binding of a receptor to a G protein causes the alpha subunit to dissociate and activate phospholipase C

phospholipase C generates DAG and IP3

24
Q

Describe the structure of a trimeric G protein

A

3 subunits - alpha, beta and gamma

binds guanine nucleotides (GTP/GDP) - hence the name G proteins

GDP is swapped to GTP NOT phosphorylated

25
Q

How is G protein reset?

A

alpha subuints have intrinsic GTPase activity

hydrolyse bound GTP to GDP and Pi

alpha subunit can re-associate with Gbeta-gamma to reform the trimeric protein

26
Q

What is the effect of Gi on adenylyl cyclase?

A

Gi = INHIBITION

decrease in cAMP

(alpha -2 adrenergic receptor)

27
Q

What is the mechanism of action of Gq?

A

stimulates phospholipase C

leads to increase in DAG snd IP3

(alpha -1 adrenergic receptor)

28
Q

What is signal transduction?

A

the process of the effector molecule binding to the receptor and triggering a chain of events that amplifies the initial signal

29
Q

What are the three ways in that termination of the signal transduction cascade can occur?

A

eliminate extracellular ligand

deactivate signal transduction proteins

remove activated receptor by endocytosis

30
Q

How is the binding affinity for a ligand measured?

A

Kd = concentration of ligand at which half the receptors are bound

31
Q

How to ion channel-linked receptors work?

A

binding of a ligand causes a shape change allowing an ion to flow across plasma membrane

32
Q

How does a nuclear hormone receptor work?

A

ligand passes through plasma membrane (non-polar) and binds receptor in cytoplasm

receptor hormone complex move to nucleus and bind specific regions of DNA found in gene promotors to elicit a biological response

(ligand can sometimes bind to receptor inside nuclear membrane)

33
Q

What kind of hormones do nuclear receptors sense?

A

steroid and thyroid hormones (non-polar)

34
Q

What can nuclear receptors also be classified as?

A

transcription factors

they have the ability to bind directly to DNA and regulate adjacent genes

35
Q

What protein kinase does DAG activate?

A

protein kinase C

  1. ligand activates receptor
  2. phospholipase C is activated
  3. PIP2 is cleaved into DAG and IP3
  4. DAG activates PKC
  5. IP3 triggers release of Ca2+ from ER
36
Q

What is the mechanism of action of IP3?

A
  1. released as soluble structure in the cytosol after breakdown of PIP2
  2. diffuses through the cytosol and binds to IP3 receptors, particularly Ca2+ channels in the smooth ER
  3. changing the cytosolic level of Ca2+causes a cascade of other intracellular activity
37
Q

What are the two classes of hormone?

A

steroid hormones - use intracellular receptors

polypeptide hormones (includes cytokines and growth factors) - use extracellular receptors ‘first messengers’

38
Q

How does NO cause smooth muscle relaxation?

A
  1. activates guanylate cyclase
  2. increased intracellular concentration of cGMP
  3. activates protein kinase G (PKG)
  4. PKG activates myosin light chain phosphatase
  5. myosin light chains are dephosphorylated leading to smooth muscle relaxation
39
Q

What do the alpha - 1 receptors activate?

A

phospholipase C

increase intracellular concentrations of DAG and IP3

40
Q

What do alpha 2 receptors do?

A

inhibit adenylyl cyclase

beta receptors stimulate it

PCS Unit 3 - Communication and Control (15 decks)

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