Lecture 8: CSF Cell Signalling Flashcards

1
Q

What are the two types of cell signalling?

A

Local signalling

Long distance signalling

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2
Q

What is local signalling?

A

Cell signalling where signals cat on nearby target cells

e.g. neurotransmitters such as acetylcholine

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3
Q

What is long distance signalling?

A

Signals that act from a distance - hormones produced by cells travel via circulatory system to act on specific cells

e.g. insulin from beta cells in pancreas

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4
Q

What are the 3 steps to cell signalling?

A

Reception
Transduction
Response

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5
Q

Explain the reception stage

A

Signalling protein (otherwise called primary messenger or ligand) binds to a receptor protein causing a change in shape of the receptor protein

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6
Q

Explain the transduction stage

A

The altered receptor protein activates another protein (eg G-protein). The activated protein may cause a relay of changes causing other proteins to be activated.

Each activated protein causes a series of changes - often via phosphorylation.

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7
Q

Explain the response stage

A

All activated proteins cause a certain function or functions to occur in the cell

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8
Q

What is a TARGET receptor?

A

It’s the receptor with the complementary shape to the shape of the ligand - structure determines function

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9
Q

Is the type of cell receptors specific to the type of the cell?

A

No, there may be different receptor molecules on the cell surface membrane of one cell type at different points in time

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10
Q

What are the two types of receptors?

A

Intracellular and membrane-bound/cell surface receptors

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11
Q

What are intracellular receptors?

A

Primary messenger is generally hydrophobic and small - lipid soluble.

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12
Q

What are membrane bound / cell surface receptors?

A

Primary messenger is generally hydrophilic and/or large

examples include GPCR (G protein coupled receptor) and ligand-gated ion channels

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13
Q

What are GPCRs?

A

G-protein coupled receptors are transmembrane proteins that pass through the membrane 7 times.

Its extracellular portion has ligand binding site and its inner portion has loops that interact with G proteins.

It is the target for 1/3 of all modern drugs

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14
Q

What are G proteins?

A

G proteins are molecular switches which are usually inactive when GDP is bound and then become switched on or active when bound to GTP (guanosine triphosphate)

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15
Q

How does the cell signalling process occur with G-protein coupled receptors?

A
  1. At rest, receptor is unbound and G protein is bound to GDP (inactive). The enzyme in the plasma membrane is in an inactive state.
  2. When the ligand binds to the receptor site of the protein, the receptor changes shape allowing G protein with GTP (hence active) to bind to the receptor molecule. The enzyme is still inactive at this stage.
  3. Activated G protein dissociates from receptor along with attached GTP. Enzyme is activated by the G protein to elicit a cellular response.
  4. G protein has GTPase activity (GTP is broken down into GDP and P) causing its release from the enzyme reverting back to resting state.
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16
Q

What are ligand gated ion channels?

A

A receptor protein containing a gate. Binding of ligands to the receptor causes change in shape opening the gate and allowing entry of ions.

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17
Q

What is a receptor?

A

A protein molecule which responds to a specific ligand

18
Q

What is a ligand?

A

A messenger molecule which binds to a specific receptor

19
Q

What is an ion channel?

A

A transmembrane protein through which specific ions can travel

20
Q

What is an ion channel receptor?

A

A membrane protein through which specific ions can travel, in response to ligand binding

21
Q

How does cell signalling process occur with ligand gated ion channels?

A
  1. At rest, the ligand is unbound and the gate is closed
  2. Upon ligand binding, the receptor molecule changes shape causing opening of gate allowing specific ions to enter cell.
  3. When ligand dissociates, ion channels close.
22
Q

What is an internal body system that relies heavily on ligand gated ion channels?

A

Nervous system - the transmission of action potentials across synapses occur via neurotransmitters that bind to ligands and open ion channels.

23
Q

What is protein kinase?

A

An enzyme that is able to transfer phosphate group from ATP to another protein - hence activates the subsequent protein in the transduction stage of cell signalling

24
Q

What is a phosphrylation cascade?

A

A series of reactions in which inactive protein kinase molecules are activated via the transfer of phosphate groups from ATP to the protein kinase. Ultimately leads to the activation of a protein that will cause a cellular response.

25
Q

What is phosphatases?

A

Enzymes that dephosphorylate rendering the protein inactive, but recyclable

Allows inactivation of protein kinase when transduction is not required

26
Q

What are the amino acids that are often phosphorylated? What is the significance of this?

A

Serine and threonine - this means mutations affecting these residues could be detrimental

27
Q

What is cAMP?

A

Cyclic adenosine monophosphate are small molecules that act as second messengers. Enzymes called adenylyl cyclase that are activated as part of GPCR signalling cause the ATP molecules to convert to cAMP which activate downstream proteins (may cause phosphorylation cascade)

28
Q

What is the enzyme that converts ATP to cAMP when activated?

A

Adenylyl cyclase

29
Q

What are examples of secondary messenger molecules?

A

cAMP and calcium ions

30
Q

Where are calcium ions found within the cell?

A

The lumen of the ER

Matrix of mitochondria

31
Q

How does the concentration of calcium ions compare inside and outside of the cell?

A

Low calcium ion concentration inside and high calcium ion concentration outside

32
Q

Why is important for the concentration difference of calcium ions to be maintained?

A

Calcium ions have signalling roles and can hence damage cells if difference is not maintained by calcium pumps.

33
Q

How does GPCR cell signalling occur with calcium ions as secondary messengers?

A

The activated G protein (GTP bound) activates an enzyme called phospholiapse C which alters PIP2 (phospholipid) to IP3 (secondary messenger)

IP3 binds to a gated channel in the ER causing the outflow of calcium ions which activate proteins in the cytosol causing cellular response.

34
Q

What is phospholipase C?

A

An enzyme part of the GPCR signalling for calcium ions. When activated, it cleaves PIP2 (a phospholipid) forming DAG and IP3 (secondary messenger)

35
Q

What is IP3?

A

Formed from PIP2, it binds to receptor proteins in the ER opening calcium ion gates.

36
Q

What is the significance of having so many stages to cell signalling?

A

Amplifies the response
Provides multiple points of control
Allows for specific responses via temporal and spatial organisation despite common molecules
Allows for coordination of signalling pathways

37
Q

What are examples of cellular responses that occur as a result of cell signalling?

A

Gene expression

Alteration of protein function 
Opening closing ion channels
Alteration of cell metabolism
Regulation of cellular organelles 
Rearrangement/movement of cytoskeleton
38
Q

Are signals permanent?

A

They only occur for limited amounts of time - activation promotes the start of deactivation ensuring homeostatic equilibrium

39
Q

What is phosphodiesterase (PDE)?

A

An enzyme that breaks down cAMP disabling (turning off) some signalling pathways

40
Q

Why do you feel wired after intake of caffeine?

A

Caffeine inhibits the action of phosphodiesterase meaning deactivation of certain signalling pathways cannot occur.

41
Q

How does adrenaline enhance ability to fight or flight?

A

Adrenalin acts through G protein coupled receptors which activate adenylyl cyclase creating cAMP. THe cAMP then works with two protein kinase molecules creating a phosphorylation cascade amplifying the signal. Hence, 1 adrenalin molecule can cause the cellular response of 100 million active glycogen phosphorylase converting many glycogen to glucose-1-phosphate. These glucose-1-phosphate can be converted to glucose-6-phosphate and used in glycolysis to produce ATP.

42
Q

How do viruses work?

A

They have surface proteins complementary to specific cell receptors which enable them to enter the cell and replicate.