(2e Communication within multicellular organisms)

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Transcript (2e Communication within multicellular organisms)

AH Biology: Unit 1
Communication Within
Multicellular Organisms
Communication within
multicellular organisms
- General principles.
- Hydrophobic signals and control of
transcription.
- Hydrophilic signals and transduction.
In animals communication is mediated by
nervous transmission and hormonal secretion.
Nervous
communication
Hormonal
communication
Nature of signal
Electrical impulses Extracellular
and extracellular
signalling
signalling molecules molecules
Transmission of
signal
Along the axons of
neurons
Through the
bloodstream
Target cells
Any cells with
connections to
neurons (effectors)
Almost any cells
in the body
Time for response Faster
to occur
Slower
Duration of
response
Longer lasting
Transient
Extent of response Localised
Widespread
Coordination is important for
homeostasis
Coordination allows integrated homeostatic
responses to be made.
Disturbances
Coordinated responses
Controlled
system
Monitoring
centres
Error
signal
Set point
values
Errorcorrecting
mechanisms
Coordination of responses allows animals to
cope with physiological stress, eg a human
doing exercise.
.
.
Exercise
• Cardiovascular challenge
• Ventilatory challenge
• Metabolic challenge
• Thermoregulatory challenge
• Osmoregulatory challenge
Extracellular signalling
Signalling cells
Specific signalling molecules released as a
result of a change in internal state
Signalling molecules carried to target cells
Target cells
Arrival of signalling molecules at target cells is
linked to a change in the internal state of the
cells (cell response)
Extracellular signalling
Signalling cells
Specific signalling molecules released as a
result of a change in internal state
Signalling molecules carried to target cells
Target cells (may also act as signalling cells)
Arrival of signalling molecules at target cells is
linked to a change in the internal state of the
cells (cell response)
Different cell types produce specific signalling
molecules.
Spatial organisation of signalling molecules
Eukaryotic cell: 50 μm
Distance: 1 nm
1 μm
1 mm
1m
1 km
Animal pheromones
Hormones
Neurotransmitters
How does a target cell ‘know’ that it
should respond to a specific signal?
Cells can only detect and respond to signals if they
possess a specific receptor.
Adrenaline
Adrenaline
receptor
protein
Insulin
Insulin
receptor
protein
Different cell types may show a specific tissue response
to the same signal.
Betareceptor
Adrenaline
Amylase release stimulated
Cell in mammalian
salivary gland
Betareceptor
Adrenaline
Glycogen breakdown
stimulated
Cell in mammalian liver
Hydrophobic signals and control of
transcription
Action of hydrophobic signalling molecules
Hormone
Intracellular
receptor protein
Altered rate of protein
synthesis (long-lasting
effects)
Altered rate of gene
transcription
Hydrophobic signalling molecules can bind
to nuclear receptors to regulate gene
transcription.
Animation of regulation of transcription.
Steroid hormones are hydrophobic signalling
molecules.
Animation of mechanism of steroid
hormone action.
The steroid hormone receptor proteins are
transcription factors.
Inhibitory protein complex
Inactive
transcription
factor
Hormone-binding
site
Steroid
hormone
Active
transcription
factor
DNA-binding site
exposed
Thyroxine is a hydrophobic hormone that
regulates the metabolic rate.
Why is thyroxine not classified as a
carbohydrate, lipid or protein?
Thyroxine is released from the thyroid gland.
Thyroxine absent
Thyroid receptor protein
bound to DNA
Transcription of Na+/K+
ATPase gene inhibited
Action of thyroxine
Thyroxine
Receptor protein
undergoes
conformational
change
Synthesis of Na+/K+
ATPase
Transcription of
Na+/K+ATPase gene
More Na+/K+ATPases
in cell membrane
Insertion into
membrane
ATP degraded
faster
Increased
metabolic rate
Synthesis of Na+/K+ ATP
Transcription of
Na+/K+ATPase gene
Hydrophilic signals and
transduction
Hydrophilic ligands
- Molecules that bind to sites on target proteins
(receptors) at the surface of cells to trigger
signal transduction.
- Ligand binding triggers the receptor protein to
undergo a conformational change.
Hydrophilic signal
Reception + transduction
Amplification
Second messenger
Internal regulator
Tissue-specific effectors
Cell responses
Action of hydrophilic signalling molecules
Hormone (ligand)
Receptor protein
Signal
transduction
Cell responses
(short-lasting
effects)
Peptide hormones are short chains of amino
acids.
• ADH
• Insulin
Neurotransmitters are chemical signals
released from nerve endings that alter the activity
of target cells.
Axon
Neurotransmitter substance
Synapse
Location of receptors
Animation of action of
acetylcholine.
Hydrophilic signal transduction 2: receptors
with kinase activity
Part of receptor
that binds insulin
(alpha-subunit)
Part of receptor
with kinase activity
(beta-subunit)
Hydrophilic signal transduction 1: G-protein
cascade
Signal
Adenylate cyclase
enzyme
Stimulatory Gprotein
cAMP (second
messenger)
Animation of G-protein activation.
Signal
Inhibitory Gprotein
Protein
kinase A
Membrane channels +
pumps, microtubules,
histones, specific
enzymes
1. Insulin binds to
receptor
2. Kinase enzyme
phosphorylates itself
(autophosphorylation)
3. Receptor
phosphorylates
insulin receptor
substrate (IRS-1)
P
P
P
P
4. Phosphorylated IRS-1
acts on effectors to trigger
cell responses
P
Animation of protein kinase activity triggered by adrenaline and tyrosine kinase activity.
Insulin regulates the glucose concentration
of the blood
Beta-cells in
pancreas
release more
insulin
Insulin
transported in
blood
ADH acts on
adipose, liver and
muscle cells
Blood glucose
concentration at
set point
More glucose is
taken up by cells
Blood glucose
concentration falls
Change detected
Blood glucose
concentration
rises
Action of insulin on fat and muscle cells
GLUT4
Animation of insulin action.
GLUT4 recruitment is also induced by exercise.
Diabetes mellitus
• A disease caused by defects in the insulin
signalling system.
• Two types of diabetes mellitus are recognised.
• What are the general symptoms of diabetes
mellitus?
Cause
Usual age of
onset
Nature of
defect
Treatment
Type 1: Insulindependent diabetes
Destruction of betacells in pancreas by
immune system
Childhood
Type 2: Non-insulindependent diabetes
Exact cause unknown
Obesity is a risk factor
Pancreas does not
produce any insulin
Target cells develop
insulin resistance
Loss of receptor
function
Eat less sugar and
saturated fat
Regular exercise
Medication to lower
blood glucose
concentration
Daily insulin injections
and management of
diet to control blood
glucose concentration
Adulthood
Global prevalence of diabetes mellitus
Numbers are millions!
Review of diabetes mellitus
- Animation of insulin production and type 1
diabetes mellitus.
- Basic animation of type 2 diabetes
mellitus.
- Animation of type 2 diabetes mellitus.
Terrestrial vertebrates require mechanisms
for conserving water
Thank goodness
I can make
ADH!
ADH regulates the body’s water balance
Pituitary gland
releases more
ADH
ADH transported
in blood
ADH acts on kidney
collecting ducts
Change detected
Blood water
concentration
rises
Blood water
concentration at
set point
More water
reabsorbed into blood
Less urine made
Blood water
concentration falls
Mechanism of action of ADH
Lumen of
collecting
duct
Collecting duct
cell
Blood
2. ADH receptor
H2O
1. ADH
5. Fusion of
vesicles
containing
AQP2 water
channel
proteins
4. Protein
phosphorylation
3. Activation of
protein kinase A
Aquaporins are protein channels that allow
efficient transmembrane movement of water.
Animation of water movement through an aquaporin channel.
Diabetes insipidus
• Disease in which the water conservation
mechanism of the kidneys fails.
• What could the nature of the failure be?
• What would the symptoms of diabetes
insipidus be?
The two types of diabetes insipidus
• Central diabetes insipidus: insufficient
ADH is produced.
• Nephrogenic diabetes insipidus: cells in
the lining of the collecting duct are unable
to respond to ADH.
Possible causes of diabetes insipidus
Lumen of
collecting
duct
Collecting duct
cell
Blood
ADH receptor
AQP2
ADH
Phosphorylated
target proteins
Protein kinase A
Symptoms of diabetes insipidus
- Excessive thirst.
- Production of large quantities of dilute
urine (‘insipidus’ = lacks flavour).
Overview of the action of ADH