Cell Signalling Flashcards

1
Q

Why do cells need to communicate?

A
1. Process Information
Sensory stimuli - e.g. light
2. Self Preservation - protection from danger
Spinal reflexes 
Sympathetic nervous system
3. Voluntary Movement
4. Homeostasis
Thermoregulation 
Glucose homeostasis
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2
Q

What are the 4 types of cell signalling.

A
  1. Endocrine signalling
  2. Paracrine signalling
  3. Signalling between membrane attached proteins
  4. Autocrine signalling
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3
Q

What is endocrine signalling?

A

Intercellular type of signalling

Hormones used to communicate - travels via the blood and acts on a distant target cell

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4
Q

What is hypoglycaemia?

A

Low blood sugar (glucose) levels

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5
Q

How does the body regulate hypoglycaemia?

A

Glucagon is secreted by the alpha cells in the islets of Langerhans
Stimulates gluconeogenesis and glycogenolysis in the liver

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6
Q

What are some other examples of endocrine cell signalling?

A

Adrenaline - fight or flight (increasing breathing and heart rates)
Insulin - produced by the beta cells in the islets of Langerhans in the pancreas, which act on the liver, muscle cells and adipose tissue

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7
Q

What is paracrine signalling?

A

Hormones acting on adjacent cells

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8
Q

What is hyperglycaemia?

A

High blood sugar levels

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9
Q

How is hyperglycaemia regulated?

A

Insulin is secreted by the beta cells in the islets of Langerhans (pancreas)
It has endocrine effects: stimulates glucose uptake
It also has paracrine effects: It inhibits glucagon secretion by nearby alpha cells

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10
Q

What are some other examples of paracrine signalling systems?

A

Nitric oxide - prevents the contraction of the smooth muscle in blood vessel and so acts as a vasodilator

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11
Q

What is signalling between membrane attached proteins?

A

Plasma membrane proteins on adjacent cells binding together/interacting

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12
Q

What are some examples of signalling using membrane attached proteins (i.e. glycoproteins)?

A

E.g. immune system - when blood borne viruses are detected and engulfed by antigen presenting cells (APCs), which digests the pathogen and expresses the antigens on its cell surface so circulating T cells can bind.
HIV - glycoproteins bind to CD4 receptors on T cells, used to get into cells
Bacterial cell wall components bind to toll-­‐like receptors on haematopoietic cells
Coagulation is platelet receptors attaching together

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13
Q

What is autocrine signalling?

A

Signalling molecule acts on same cell - i.e secreted by a cell and acts on itself
Used for feedback loops

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13
Q

What are the 4 types of post synaptic receptors?

A

1234

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14
Q

What are some examples of autocrine signalling?

A

Activated T-cell receptor (TCR) will initiate a cascade of reactions within T-cell
Activated T-cell expresses interleukin-2 (IL-2) receptor on surface
Activated T-lymphocyte also secretes IL-2, which:
1. Binds to IL-2 receptor on same cell
2. Binds to IL-2 receptor on adjacent activated T-cell
[ Acetylcholine binds to pre­‐synaptic muscarinic receptors (negative system)
Growth factors from tumour cells can lead to mitogenesis in the tumour cell ]

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15
Q

What are the 4 types of post synaptic receptors?

A

Ligand and neurotransmitters are the same thing!

  1. Ionotropic Receptor ‐ ligand binding opens an ion permeable pore
  2. G-­protein coupled receptor ‐ ligand binding activates intracellular G ‐ protein•Enzyme linked receptor-­‐ligand binding leads to receptor clustering which activates internal enzymes•Intracellular Receptor-­‐a membrane permeable ligand binds to a receptor inside the cell
17
Q

How does the ionotropic receptor work? [Signal Transductional Events]

A

Ligand binds to the receptor protein
Change in conformation of channel protein, opening of a pore
Pore allows ions to move in or out of cell according to their respective concentration gradients

18
Q

What are some examples of ionotropic receptors?

A

E.g. Nitcotinic acetylecholine receptor - located on skeletal muscle at neuromuscular junctions, acetylcholine binds, and it begins the depolarisation which leads to muscle contraction
GABA - Located on many cells in the CNS, allows transmission of anions. GABA binds to the receptor and causes the opening of the pore which allows an influx of chloride ions, causes a depression activity. If you block the GABA receptor you get hyperexcitability of the CNS and possibly epileptic seizures

19
Q

How does the G-protein coupled receptor work? [Signal Transductional Events]

A

GPCR is also called 7-TM (7 transmembrane)
G-protein exists as a heterotrimer - 3 subunits, alpha, beta and gamma
Ligand binding causes conformational change of the receptor
Allows unassociated G-protein to bind to the internal surface of the GPCR
GDP is exchanged for GTP
GTP provides energy for G-protein to dissociate into two active components: alpha and beta-gamma
Both bind to their target cells respectively
Once the alpha subunit has attached to the target protein, internal GTPase activity within the subunit causes the GTP molecule to change to a GDP molecule
Allows the alpha subunit to unbind from the target protein and reform the heterotrimer with GDP attached

20
Q

How long does the G-protein coupled receptor stay active?

A

As long as ligand is bound and can activate further heterotrimeric G-proteins

21
Q

What are the 3 types of G-alpha subunit linked receptor?

A
1. Gs protein linked receptor
S = stimulatory	
2. Gi protein linked receptor
i = inhibitory
3. Gq protein linked receptor
22
Q

How does the Gs protein linked receptor work?

A

Stimulates adenylate cyclase
Adenylate cyclase converts ATP to cAMP
cAMP increases levels of PKA (protein kinase A)
Example: β1-adrenergic receptor (found on the heart)
NOTE: beta blockers act on the β1-adrenergic receptor

23
Q

How does the Gi protein linked receptor work?

A

Opposite effect to the Gs protein
Inhibits adenylate cyclase thus reducing levels of cAMP and PKA
Example: M2-muscarinic receptor

24
Q

How does the Gq protein linked receptor work?

A

Activates phospholipase C (PLC)
PLC converts PIP2 (Ohosphatidylinositol Bisphosphate) —-> IP3 + DAG
IP3 —> increase in intracellular Ca2+
DAG (Diacylglycerol) - activates PKC
Example: AT-1 angiotensin receptor (Angiotensin is a hormone produced in the kidneys which is the most potent vasoconstricter in the body)

25
Q

How does the enzyme linked receptor work? [Signal Transductional Events]

A

Ligand binds and the receptors cluster
Receptor clustering activates enzymes in the intracellular compartment
Enzymes and proteins are attracted to the receptor and move towards it to become activated
Activation of enzymes leads to phosphorylation of the receptor - which, in turn, leads to binding of signalling proteins to the cytoplasmic domain
Signalling proteins recruit other signalling proteins and a signal is generated within the cell

26
Q

What is the main enzyme associated with enzyme linked receptors and how does it work?

A

Tyrosine kinase - phosphorylates any protein which has a tyrosine amino acid within it
The signal is terminated when a phosphatase removes the phosphate group

27
Q

What are the 3 types of enzyme linked receptors?

A

Tyrosine Kinase Linked Receptor (95%)
Guanylyl-cyclase Linked Receptor
Serine-Threonine Kinase Linked Receptor

28
Q

What are some examples of enzyme linked receptors?

A
1. Insulin Receptor (CD220)
Ligand: Insulin 
Physiological effect: glucose uptake 
2. ErbB Receptor 
Big family of receptors 
Ligand: Epidermal Growth Factor, Transforming Growth Factor β 
Physiological effect: tumour genesis
29
Q

What are the 2 types of intracellular receptors and how do they work? [Signal Transductional Events]

A

Type 1: Cytoplasmic
Located within the cytoplasm
Attached to heat shock proteins
Ligands are usually steroids which pass through the membrane and act on intracellular receptors
Ligand binds to the Type 1 receptor which dissociates from the heat shock protein
The ligand and receptor move together to the nucleus
It binds to the DNA and causes increased or decreased transcription
NOTE: the type 1 intracellular receptors perform their function as homodimers - these intracellular receptors are actually transcription factors
Type 2: Nuclear
Located within the nucleus and is already bound to DNA
Ligand comes in, moves through the nuclear envelope and binds to the receptor on the DNA causing changes in transcription

30
Q

How long does it take for the effects of the intracellular receptors to show?

A

Longer than others

31
Q

What are some examples of intracellular receptors?

A

Type 1 - Glucocorticoid Receptor
Ligand: cortisol, corticosterone
Physiological Effect: Downregulate immune response, increase gluconeogenesis
Agonists: Glucocorticoids
Type 2 - Thyroid Hormone Receptor
Ligand: Thyroxine (T4), Triiodothyronine (T3)
Physiological Effect: Growth & Development
Agonists: Thyroid hormones

32
Q

SUMMARY of 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

33
Q

SUMMARY of Ion channels:

A
Ion channels, activated (‘gated’) by a ligand
Signal transduction:
Ligand binding 
Conformational change, pore opening
Ions flow through pore 
Example:
Nicotinic ACh receptor
34
Q

SUMMARY of Ion channels:

A

G-protein coupled receptors
7-TM proteins with:
Extracellular ligand-binding N-terminus
Intracellular G-protein binding C-terminus
Signal transduction:
Ligand binding, G-protein binding & phosphorylation,
G-protein uncoupling & target protein activation
Examples:
Beta-1 receptor – Gs; M2 receptor – Gi; AT-1 receptor - Gq activate

35
Q

SUMMARY of Enzyme linked & intracellular receptors:

A

Enzyme linked - signal transduction
Ligand binding, receptor clustering, activation of enzymes, phosphorylation of target proteins
Intracellular - Signal transduction
Hormone enters cell & binds, Ligand-receptor complex = transcription factors
Examples:
Glucocorticoids & Estrogen receptors