MBC - Cell Signalling Flashcards

1
Q

What is cell signalling for?

A
  • Processing information
  • Self-preservation
  • Voluntary movements
  • Homeostasis
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2
Q

What are the main 2 systems that provide lines of communication?

A
  1. Nerve fibres of CNS/PNS

2. Blood vessels of cardiovascular system

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3
Q

What are the differences in the means of communication?

A

Nerves are rapid/instantaneous

Blood is slow/versatile

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4
Q

How is action potential generated?

A

Influx of Na+
Efflux of K+
This bio-electrical current generates action potential

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5
Q

How does neurotransmitters get released from vesicles?

A
  1. Action potential arrives at presynaptic knob open voltage-gated Ca+ channels
  2. Influx of Ca+ bind to vesicles —> exocytosis
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6
Q

How neurotransmitters activate post-synaptic receptors?

A

NT bind to receptors in post-synaptic membrane and activate bio-electrical current

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7
Q

What are the 2 consequences of NT binding to post-synaptic membrane opening ion channels?

A

Depolarisation

Hyperpolarisation

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8
Q

What are the different receptors on post-synaptic membrane?

A
  • 7 transmembrane G-protein coupled receptors
  • voltage(ligand)-gated ion channels/ ionotropic receptors
  • enzyme-linked receptors
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9
Q

What are the 4 main types of hormonal communication?

A
  • Endocrine comm
  • Paracrine comm
  • Autocrine comm
  • Communication between membrane receptors
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10
Q

What is an example of endocrine comm?

A

Physiological response to hypoglycaemia
(Glucagon secreted by a-cells stimulates glycogenolysis (glycogen breakdown to glucose) & gluconeogenesis (pyruvate to glucose) in liver - to increase BGL)

  • insulin (increase glucose uptake, reduce glycogenolysis/glucogenesis)
  • adrenaline
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11
Q

What is endocrine signalling?

A

Hormone travels in blood vessel to act on distant target cell

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12
Q

What is an example of paracrine comm?

A

Physiological response to hyperglycaemia
(Insulin secreted by B-cell acts on a-cell to reduce production of glucagon)

  • nitric oxide produced by endothelial cell in blood vessel (vasodilation - septic shock)
  • osteoclast activating factors produced by adjacent osteoblasts (bone formation)
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13
Q

What is paracrine signalling?

A

When hormone acts on an adjacent cell

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14
Q

What is an example of signalling between attached proteins?

A

IMMUNE SYSTEM

  1. Blood borne virus detected by antigen presenting cell (APC)
  2. APC digests pathogen and expresses class II molecules on surface (MHC)
  3. MHC interact with circulating T-cell receptor
  • Hepatitis C
  • HIV GP120 & CD4 receptor on T-cells
  • Bacterial cell wall component & toll-like receptors on haematopoietic cell
  • corona virus & ACE2
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15
Q

What is signalling between membrane attached protein?

A

Plasma membrane proteins on adjacent cells interacting with each other

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16
Q

What is an example of autocrine signalling?

A

Activated T-cell receptor (TCR) has IL-2 receptor on surface
Secretion of IL-2 from T-cell binds to own/adjacent IL-2 receptor

  • Negative feedback responses - acetylcholine act on presynaptic M2-muscarinic receptors
  • Growth factors on tumour cells acts on itself to cause mitogenesis
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17
Q

What is autocrine signalling?

A

Signalling molecule act on the same cell (itself)

18
Q

What is Lupus?

A

Autoimmune disease

- distinguish by facial rash resembling butterfly wings across both cheeks

19
Q

What is multiple sclerosis?

A

Demyelination of nerve cells in brain and spinal cord - disrupt signal transmission

20
Q

What is myasthenia gravis?

A

Neuromuscular disease (autoimmune) antibodies destroy receptors at junction between nerve and muscle leading to skeletal muscle weakness

21
Q

What is rheumatoid arthritis?

A

Autoimmune disorder - inflammation at joints due to antibodies attacking synovium

22
Q

What are chemical messages/molecules referred as when they exert defect by binding to receptors?

A

Ligands

23
Q

What is a second messenger?

A

Chemical messenger, that evokes an intracellular effect, which is separate from the receptors or ligand

24
Q

What are the 4 categories of receptors?

A
  • Ligand-gated ion channel (ionotropic) receptors
  • G protein coupled receptors
  • Enzyme-linked receptors
  • Intracellular receptors
25
Q

How do ionotropic receptors work?

A
  1. The ligand binds to receptor protein (ligand-binding domain)
  2. Conformational changes opens pore
  3. Ions move in/out of cell according to concentration gradient
26
Q

What are some examples of ionotropic receptors?

A

Acetylcholine on skeletal muscle for muscle contraction

27
Q

What ions go through ionotropic receptors?

A

Sodium, potassium, calcium

28
Q

Why are G protein-coupled receptors known as 7 transmembrane receptors?

A

Channel protein goes through membrane 7 times

29
Q

What does a G protein complex contain?

A
  • alpha subunit
  • beta-gamma subunit
  • GDP molecule

A Heterotrimer

30
Q

What are the difference between G(alpha) subunits - associated with signal transduction pathways?

A
  • q/11: activates PLC (promote Ca+ release from stores + activate non-selective channels)
  • s: activates AC (activates PKA)
  • i/o: inhibits AC ( inhibits PKA)
31
Q

Describe the activation of G protein.

A
  1. Ligand binding causes G complex to associate with close proximity receptor
  2. GDP phosphorylation into active GTP
  3. G(alpha) subunit + GTP dissociated from G(beta-gamma) subunit - both act as secondary messengers, binds to target protein
  4. Internal GTPase dephosphorylates GTP -> GDP
  5. G(alpha) subunit becomes inactivated, dissociates from target protein
  6. Subunits re-associate to form G complex

(Cycle repeats until ligand is unbound)

32
Q

What is the structure of enzyme-linked protein?

A

One transmembrane domain; ligand-binding domain (outside), specialised enzyme (inside)

33
Q

How do enzyme-linked receptors work?

A
  1. Ligands bind to several receptors
  2. Cause receptor clustering which activate enzyme within cytoplasm
  3. Enzyme phosphorylates receptor (activated), leading to signalling to activate other parts of cell
  4. Signal stops when phosphatase dephosphorylates receptor
34
Q

What hormones and how do they bind to Intracellular receptors?

A

Steroid hormone are membrane permeable (hydrophobic, lipophilic)

35
Q

What are Intracellular receptors?

A

Transcription factors - regular mRNA & protein synthesis

36
Q

Where are the Intracellular receptors located? (Type I & II)

A

Type I - cytoplasm

Type II - Nucleus

37
Q

How do type I Intracellular receptors work?

A

Type I receptors are linked with ‘heat shock proteins HSP’ - chaperone molecules

  1. Hormones bind to receptor, type I dissociate with HSP to from hormone-receptor complex
  2. Joins with another identical hormone-receptor complex to form a HOMODIMER
  3. Homodimer translocates to nucleus, binds to DNA (as TF)
38
Q

How do Type II intracellular receptors work?

A
  1. Hormone ligand go through cell & nuclear cell membrane
  2. Bind to Type II (already bound to DNA)
  3. Cause transcription
39
Q

What are some examples of G-protein coupled receptors?

A

Beta-1 receptor: Gs
M2 receptor: Gi
AT-1 receptor: Gq

40
Q

What are some examples enzyme-linked receptors?

A

-ErbB receptors for cell growth, proliferation
Ligand: epidermal growth factor, transforming growth factor(beta)

  • insulin receptor for glucose uptake
    Ligand: insulin
41
Q

What are some examples of intracellular receptors?

A

Type I - Glucocorticoid receptors for lowering immune response/ increase gluconeogenesis
Ligand: Cortisol/corticosterone

Type II - Thyroid hormone receptors for growth and development
Ligand: Thyroxine (T4), Triiodothyronine (T3)