Cell communication and signalling Flashcards

1
Q

Learning Outcomes

A
  • Define the terms cell communication, cell signalling, signal transduction
  • List the different forms of cell communication
  • Describe the mechanisms of G-protein coupled receptor (GPCR) signalling, and the role of G-proteins Explain what second messengers are, with examples such as cAMP
  • Define the terms cell communication, cell signalling, signal transduction-List the different forms of cell communication-Describe the mechanisms of G-protein coupled receptor (GPCR) signalling, and the role of G-proteins
  • Identify how Receptor Tyrosine kinase signalling functions, and the role of tyrosine phosphorylation
  • Be able to name other forms of cell signalling such as steroid hormone andnitric oxide (NO) signalling
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2
Q

What are unicellular organisms signalling mechanism?

A

Use short peptides- responses are
Grow/divide
Die
Escape from immune cells

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3
Q

What substances do multicellular organisms signalling mechanisms use? Give examples

A

Use peptides, proteins, AA’s, nucleotides, steroids, retinoids, FA’s, gases (NO)
Can attract other cells, tell them to move away, to die, grow, divide
E.G hypoxia- cells release VEGF protein which causes blood vessel growth, leading to more oxygen supplied to organ.
E.G Knee jerk reflex- nerve/spinal signalling
E.G Neutrophil hunting bacteria

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4
Q

Examples of signalling molecules

A

See lecture 45 table

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5
Q

What is the difference between local and long distance cell signalling?

A

Local

  • contact
  • cell cell signalling
  • Paracrine- cells in same vicinity
  • Autocrine
  • Synaptic
Long distance
-Endocrine-hormonal e.g insulin, adrenaline, thyroid
- Neuronal- short and long distance- diffusion of NT across synaptic cleft to target cell, LD as nerve body can be long distance from cleft e.g breathing
phrenic nerve (neuron) and diaphragm (muscle cells, NM junction)
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6
Q

What is paracrine signalling?

A

Paracrine signaling: signaling in which the target cell is close to the signal releasing cell, and the signal chemical is broken down too quickly to be carried to other parts of the body.
example of Paracrine Signalling:
Insulin-like growth factor (IGF-1) signalling in Melanoma
Clotting agents in thrombus formation
Inflammatory mediators e.g. TNFa

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7
Q

What is autocrine signalling?

A

A form of signaling in which a cell secretes a chemical messenger that signals the same cell.
Examples of Autocrine Signaling:
-Cancer cells
-Interleukin-I (IL-1) in monocytes(immune)
-IL-2 signalingin T-cells

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8
Q

Describe the effect of insulin (endocrine signalling)

A

food >
increased blood glucose>
release of insulin from pancreas (islets of langerhans)>
insulin travels in blood to stimulate glucose uptake into blood, muscl, liver fat cells

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9
Q

How do cells achieve signalling?

A

Cells use specific receptors for cell signalling

  • response of cells depends on what receptors it expresses
  • same hormone can have different effects in different cells via the same receptor
  • each receptor is specific for its own ligand(“lock and key”)
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10
Q

Describe the basic model of signal transduction

A

Signal transduction pathways:
basic model- membrane receptors allows hydrophyllic molecules to signal to the inside of the cell
-the signal is transduced from the
outside to the inside of a cell via intracellular signalling molecules
-the signal can be fast or slow in terms of the cell responses
Fast: adrenaline action on heart cells
Slow: insulin action on liver

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11
Q

What are the advantages of ST?

A

Signal transduction allows massive amplification of the signal- This means very low amounts of hormones, neurotransmitters can be effective in the body
E.G- reception of light

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12
Q

What are the different types of cellular receptors?

A
Plasma membrane bound 
1. G-protein coupled receptors 
2. Enzyme-linked receptors
3. Ion channel receptors 
Intracellular receptors
4. Steroid hormones
Local signalling-gases Nitric oxide
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13
Q

Basic model of cell signalling from the plasma membrane

A

See lecture 45
Receptor > adaptor > effector
Receptors e.g ion channels, GPCR, receptor tyrosine kinase
Adaptors> adaptor proteins, scaffold proteins, molecular switches (messenger, amplifier and transducer proteins)
Effectors- responses ( proliferation, migration, apoptosis, transcription, glucose uptake etc.) primary messenger binds to receptor outside cell
- secondary messengers e.g cAMP brings about cellular responses

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14
Q

What are some drugs that target G protein coupled receptors (GCPR’s)?

A
  • examples of drugs that target GPCRs:
  • salbutamol (asthma)
  • b-blockers (hypertension)
  • serotonin-dopamine (L-DOPA)
  • angiotensin II blockers
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15
Q

What are GCPRs?

A

G-protein Coupled Receptors (GPCRs)-GPCRs are proteins that span the membrane 7 times-1000s of GPCRs in the body, used by diverse ligands for rapid responses-examples: adrenaline, acetylcholine, dopamine, light, olfaction
-largest drug target family in the body-1000s of receptors controlling heart rate, vision, smell

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16
Q

How do active GPCRs trigger activation of G proteins?

A
  • G-proteins are made up of a and bg subunits
  • inactive G-proteins contain GDP bound to the a-subunit
  • activation of G-proteins by GPCR swaps GDP for GTP
  • active G-protein can then activate its effector and transmit the signal-signal turned off by the hydrolysis of GTP>GDP
17
Q

How are G proteins related to second messengers?

A

G-proteins activate enzymes that generate “second messengers” in the cell
-examples of second messengers are cAMP, IP3, DAG-second messengers are small molecules with key functions inside cells

18
Q

What are enzyme coupled receptors (ReceptorTyrosineKinases)?

A
  • receptors form dimers that span the PM once
  • receptors are enzymes that phosphorylate tyrosine amino acids (the “on switch”)
  • RTKs used by insulin, growth factors, EPO etc.

RTKs are enzymes that control cell growth, cell division “slower” cellular responses
-many growth factors involved in tumour formation (EGF, VEGF)

19
Q

How do RTK’s activate effector enzymes?

A

Receptor Tyrosine Kinases activate effector enzymes directly

  • on/off switch for RTKs depends on phosphorylation of tyrosine
  • enzymes activated by RTK include MAPK, PI3K, Akt (ECB p557-559)
20
Q

What are ion channels role in cell communication?

A

Some ion channels are receptors for extracellular ligands

  • channels for Na+, K+, Ca 2+ etc can be activated by ligand binding
  • ion channels are receptors for acetylcholine, glycine, GABA
21
Q

What is the difference between GCPR and RTK?

A

GCPR- 1000’s of receptors

  • diverse ligands
  • 7 transmembrane domains
  • Regulation of effectors eg. AC,PLC, ion channels
  • Rapid responses
  • Physiological examples: Adrenaline: heart rate, Smell food: salivate

RTK- Single transmembrane domain, activated by dimerisation

  • Direct regulation of effectors eg PI3K
  • Coupling to adaptor and scaffold proteins to transmit the signal e.g MAPK- Slower responses
22
Q

What is Nitric Oxide and its role in communication?

A

NO- Diffuses rapidly to paracrine cells and triggers smooth muscle relaxtion.
Target is guanylyl cyclase, generating cGMP and this causes vasodilation.