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POM Molecular Biology of the Cell > Cell Signaling > Flashcards

Cell Signaling Flashcards

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1
Q

What are the four reasons we need cell signalling?

A
  1. To process information
  2. For self preservation
  3. For voluntary movement
  4. For homeostasis
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2
Q

What is meant by self-preservation?

A

The activation of the reflex arc to protect ourself from danger

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3
Q

What are the two systems which provide the main lines of communication?

A

Nerve fibers of the central and peripheral nervous system

Blood vessels of the cardiovascular system

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4
Q

What line of communication is used for a rapid, instantaneous response?

A

The nerve fibres of the CNS and PNS

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5
Q

What line of communication is slower and more versatile?

A

The blood vessel system

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6
Q

What is meant by intercellular signalling?

A

Signalling between cells

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7
Q

What is meant by intracellular signalling?

A

Signalling within a cell

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8
Q

What are the four methods of signalling?

A
  1. Autocrine
  2. Endocrine
  3. Paracrine
  4. Communication between membrane attached proteins
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9
Q

What is meant by endocrine communication?

A

Hormone travels in the blood vessel and acts on a DISTANT target cell

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10
Q

How does glucagon act as an example of endocrine signalling?

A

Glucagon is released by the alpha cells of the Islets of Langerhans, and then transported in the blood to act on the liver, to stimulate glyconeogenesis and glycogenolysis to make more glucose

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11
Q

How does insulin provide an example of endocrine communication?

A

Insulin produced by the pancreas acts on muscle and adipose tissue

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12
Q

How does adrenaline provide an example of endocrine communication?

A

Produced by the adrenal glands and travels in the blood to act on many body systems like the lungs and trachea

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13
Q

What type of communication is shown in response to hypoglycaemia?

A

Endocrine

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14
Q

What type of communication is shown in response to hyperglycemia? and why

A

Paracrine and Endocrine - when blood glucose levels are too high, insulin is released which inhibits the secretion of glucagon from the alpha islet cells
Endocrine effects on the liver ie reduced glycogenolysis

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15
Q

What is meant by paracrine communication?

A

Hormone acts on an ADJACENT cell

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16
Q

How does the pancreas show paracrine communication?

A

Insulin produced by the Beta cells acts on the Alpha cells of the islet of langerhans to inhibit glucagon production

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17
Q

Describe how nitric oxide acts in a paracrine manner.

A

Nitric Oxide produced by the endothelium in blood vessels, acts on the smooth muscle to vasodilate the vessels

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18
Q

How do osteoclasts act in a paracrine manner?

A

Osteoclast activating factors produced by adjacent osteoblasts

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19
Q

What is meant by membrane attached protein comunication?

A

Plasma membrane proteins on adjacent cells interacting

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20
Q

Describe an immunological example of membrane-attached protein communication. (involving APCs)

A

1) Blood borne virus (e.g. hepatitis C) is detected within blood stream by antigen presenting cell (APC)

2) The antigen presenting cell (APC) digests the pathogen –> expresses major histo-compatibility (MHC) class II molecules on surface

3) Circulating T-lymphocytes engages with MHC molecule through T-cell receptor (TCR) interaction

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21
Q

How does HIV glycoproteins and bacterial cell wall components have “signalling between membrane attached proteins”?

A

→ HIV GP120 glycoprotein –> CD4 receptors on T-lymphocytes

→ Bacterial cell wall components –> toll-like receptors on haematopoietic cells

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22
Q

What is meant by autocrine communication?

A

Signalling molecules acts on same cell

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23
Q

How do T cells display autocrine forms of communication?

A

1) Activated TCR will initiate a cascade of reactions within T-cell
4) Activated T cell expresses interleukin-2 (IL-2) receptor on surface
3) Activated T-lymphocyte also secretes IL-2 which…
- Binds to IL-2 receptor on same cell
- Binds to IL-2 receptor on adjacent activated T-cell
- Which mediates cytokine release

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24
Q

How does acetylcholine and growth factors act in an autocrine manner?

A

Acetylcholine –> presynaptic M2- muscarinic receptors

Growth factors (e.g. TGFbeta) from tumour cells (mitogenesis)

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25
Q

What are the overall types of signalling?

A

Endocrine: blood vessels-> distant target cell

Paracrine: hormone acts on adjacent cell

Membrane attached proteins: plasma membrane proteins on adjacent cells interacting

Autocrine: signalling molecule acts on same cell

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26
Q

Describe how neurotransmission occurs?

A

1) Propagation of the action potentials (AP)
- Action potentials are propagated by VGSCs (voltage gated sodium ion channels) opening
- Na+ influx –> membrane depolarisation –> AP ‘moves along’ neurone
- Voltage gated potassium ion channels opening –> K+ influx –> repolarisation

2) Neurotransmitter (NT) releases from vesicles
- Action potential opens voltage-gated Ca2+ channels at presynaptic terminal
- Ca2+ influx –> vesicle exocytosis

3) Activation of postsynaptic receptors
- Neurotransmitter binds to receptors on post-synaptic membrane
- Receptors modulate post-synaptic activity

4) Activation of postsynaptic receptors
- The signal can be transmitted by a variety of different types of receptor…

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27
Q

What are the four distinct categories of receptors which exist?

A

1) Ionotropic receptor
- Ligand binding –> opens ion permeable pore traversing the membrane

2) G protein coupled receptor
- Ligand binding –> activates intracellular G-protein

3) Enzyme-linked receptor
- Ligand binding –> receptor clustering –> activates internal enzymes

4) Intracellular receptor
A membrane permeable ligand binds to receptor inside cell

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28
Q

How do ionotrophic receptors work?

A

Signal transduction events…
1) Ligand binds to the receptor protein
2) Change in conformation of channel protein –> opening of a pore
3) Pore allows ions to move in or out of cell according to their respective concentration gradients

E.g.
- Nicotine acetylcholine
Ligand: acetylcholine (ACh)
Location: skeletal muscle
Physiological effect: muscle contraction

29
Q

How is the direction of the movement of ions through ionotrophic receptors determined?

A

Through concentration gradients

30
Q

What is an example of an ionotrophic receptor?

A
  • Nicotine acetylcholine
    Ligand: acetylcholine (ACh)
    Location: skeletal muscle
    Physiological effect: muscle contraction
31
Q

What is the ligand for NMDA receptors?

A

Glutamate

32
Q

What is the ligand for GABA alpha receptors?

A

GABA

33
Q

What are G-coupled receptors also known as?

A

7-TRANSMEMBRANE RECEPTORS

34
Q

In resting state what does the G protein complex consist of?

A

The Ga subunit, a GBγ subunit and an associated GDP molecule

35
Q

Describe how G couples receptors work/ What are the signal transduction events?

A

1) 7-TM receptor and heterotrimeric G-protein are inactive

2) Ligand binding –> changes conformation of receptor

3) Unassociated G-protein binds to the receptor –> bound GDP molecule is phosphorylated to GTP
- GDP is exchanged for GTP

4) G-protein dissociates into 2 active components:
i. Alpha subunit
ii. Beta gamma subunit
–> bind to their target proteins

5) Internal GTPase activity on alpha subunit dephosphorylates GTP–> GDP

6) Alpha subunit dissociates from target protein –> inactive again

7) Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins

36
Q

What is stimulated to convert ATP to cAMP?

A

AC - Adenylyl cyclase

37
Q

What is cAMP?

A

Cyclic Adenosine monophosphate

38
Q

What does cAMP activate?

A

Protein kinase A

39
Q

Which g protein linked receptor activates adenylyl cyclase?

A

G s protein linked receptor

40
Q

Which g protein linked receptor inactivates adenylyl cyclase?

A

Gi protein linked receptor

41
Q

What is an example of a G protein linked receptor which stimulates adenylyl cyclase?

A

B1 - adrenergic receptor

42
Q

What is an example of a G protein linked receptor which inacitaves adenylyl cyclase?

A

M2 - muscarinic receptor

43
Q

What does the Gq protein linked receptor do?

A

Stimulates phospholipase C (PLC)

44
Q

Give overviews of the 3 types of G protein linked receptors.

A

1. Gs protein linked receptor
Stimulates adenylyl cyclase

  • Converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP)
  • cAMP activates protein kinase A (PKA)
    Example: b1-adrenergic receptor

2. Gi protein linked receptor
Inhibits adenylyl cyclase

  • Reduces levels of PKA
    Example: M2-muscarinic receptor

3. Gq protein linked receptor
Stimulates phospholipase C (PLC)

  • Converts PIP2 to IP3 and DAG
  • IP3 stimulates Ca2+ release
  • DAG activates PKC
    Example: AT-1 angiotensin receptor
45
Q

How do enzyme linked receptors work?

A
  1. Ligand binds to receptor
  2. This results in receptor clustering
  3. The clustering activates enzyme activity within cytoplasmic domain
  4. The enzymes which are activated then phosphorylate the the receptor which leads to the binding of signalling proteins in the cytoplasmic domain
  5. These signalling proteins recruit other signalling proteins and a signal is generated within the cell.
  6. The signal is terminated when a phosphatase dephosphorylates the receptor.
46
Q

What are the possible enzyme linked receptor pathwyas that can be activated?

A

PLC–> DAG–> PKC

Ras/ Raf/ Mek–> ERK1/2

JAK–> STAT

pAKT–> mTOR/ NFkb/ CREB

47
Q

What enzyme is activated when insulin binds to the insulin receptor?

A

Tyrosine kinase

48
Q

What enzyme is activated when ANP and BNP bind o the NPR1 receptor?

A

Guanylyl Cyclase

49
Q

What is the ligand and physiological affect of the ErbB receptor?

A

Epidermal growth factor , transforming growth factor beta

Cell growth, proliferation

50
Q

What enzyme is activated when TGR Beta binds to TGF B receptors?

A

Ser/Thr kinase

51
Q

What is the physiological effect of Set/Thr kinase activation?

A

Apoptosis

52
Q

What is the physiological effect of activation of Tyrosine kinase?

A

Glucose uptake and lipid metabolism

53
Q

What is the physiological effect of activation of guanylyl cyclase?

A

Vasodilation and reduction in blood pressure

54
Q

Where are type 1 intracellular receptors located?

A

Within the cytosolic compartment/ cyotplasmic

55
Q

Where are type 2 intracellular receptors located?

A

In the nucleus/ nuclear

56
Q

How do type 1 intracellular receptors work?

A

Type 1- Cytoplasmic
1) Located within cytosolic compartment
2) Associated with chaperon molecules (heat shock proteins, hsp)
3) Hormone binds to receptor –> hsp dissociates
4) 2 hormone bound receptors form a homodimer
The homodimer translocates to the nucleus –> binds to DNA

57
Q

How do type 2 intracellular receptors work?

A

Type 2- Nuclear
1) Located within the nucleus
Binding of hormone ligand –> transcriptional regulation

58
Q

What chaperone molecules are type 1 intracellular receptors normally associated with?

A

hat shock proteins

59
Q

What is an example of a type 1 intracellular receptor?

A

Glucocorticoid receptor

60
Q

What ligands binds to the glucocorticoid receptor?

A

Cortisol and corticosterone

61
Q

Physiological effect of cortisol binding to glucocorticoid receptor?

A

Reduced immune response and increased gluconeogenesis

62
Q

What is an example of a type 2 intracellular receptor?

A

Thyroid hormone receptor

63
Q

What is the associated ligand for the thyroid hormone receptor and what is the physiological effect?

A

Thyroxine and triiodothyronine (T4 and T3)

Growth and development

64
Q

With type II intracellular receptors, what causes the direct transcriptional regulation?

A

Activated hormone-receptor complex

65
Q

What is a homodimer?

A

When two identical hormone receptor complexes join

66
Q

Intracellular receptors are essentially what?

A

Transcription factors

67
Q

Why do steroid hormones extert their actions on intracellular receptors?

A

They are membrane permeable

68
Q

When the hormone binds to the receptor, what dissociates?

A

The heat shock protein

69
Q

What is a ligand?

A

A molecule that binds to a receptor to exert a specific effect

POM Molecular Biology of the Cell (15 decks)

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