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 and extracellular signalling molecules

Extracellular signalling 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 to occur

Faster Slower

Duration of response

Transient Longer lasting

Extent of response Localised Widespread

Coordination is important for homeostasis

Coordination allows integrated homeostatic responses to be made.

Monitoring centres

Controlled system

Error- correcting mechanisms

Set point values

Disturbances

Error signal

Coordinated responses

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 cellsArrival 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

Hormones

Neurotransmitters

Animal pheromones

Eukaryotic cell: 50 μm

Distance: 1 nm 1 μm 1 mm 1 m 1 km

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.

InsulinAdrenaline

Insulin receptor protein

Adrenaline receptor protein

Different cell types may show a specific tissue response to the same signal.

Beta-receptor

Adrenaline Beta-receptor

Adrenaline

Cell in mammalian salivary gland

Cell in mammalian liver

Amylase release stimulated Glycogen breakdown stimulated

Hydrophobic signals and control of transcription

Action of hydrophobic signalling molecules

Altered rate of gene transcription

Altered rate of protein synthesis (long-lasting effects)Intracellular

receptor protein

Hormone

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.

Hormone-binding site

DNA-binding site exposed

Inhibitory protein complex

Inactive transcription factor

Active transcription factor

Steroid hormone

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

Transcription of Na+/K+ ATPase gene inhibited

Thyroid receptor protein bound to DNA

Action of thyroxine

Transcription of Na+/K+ATPase gene

Synthesis of Na+/K+

ATPase

Receptor proteinundergoes conformational change

Thyroxine

Transcription of Na+/K+ATPase gene

Synthesis of Na+/K+ ATPase

More Na+/K+ATPases in cell membrane

Increased metabolic rate

ATP degraded faster

Insertion into membrane

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

Receptor protein

Hormone (ligand)

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.

Animation of action of acetylcholine.

Location of receptors

Axon

Synapse

Neurotransmitter substance

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

Animation of G-protein activation.

Signal Signal

Stimulatory G-protein

Inhibitory G-protein

Adenylate cyclase enzyme

cAMP (second messenger)

Protein kinase A

Membrane channels + pumps, microtubules, histones, specific enzymes

Animation of protein kinase activity triggered by adrenaline and tyrosine kinase activity.

2. Kinase enzyme phosphorylates itself(autophosphorylation)

1. Insulin binds to receptor

P

P

P

P

P

3. Receptor phosphorylates insulin receptor substrate (IRS-1)

4. Phosphorylated IRS-1 acts on effectors to trigger cell responses

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

More glucose is taken up by cellsBlood glucose concentration falls

Blood glucose concentration at set point

Blood glucose concentration rises

Change detected

Action of insulin on fat and muscle cells

Animation of insulin action.

GLUT4

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?

Type 1: Insulin-dependent diabetes

Type 2: Non-insulin-dependent diabetes

Cause Destruction of beta-cells in pancreas by immune system

Exact cause unknownObesity is a risk factor

Usual age of onset

Childhood Adulthood

Nature of defect

Pancreas does not produce any insulin

Target cells develop insulin resistanceLoss of receptor function

Treatment Daily insulin injections and management of diet to control blood glucose concentration

Eat less sugar and saturated fatRegular exerciseMedication to lower blood glucose concentration

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

More water reabsorbed into bloodLess urine madeBlood water concentration falls

Blood water concentration at set point

Blood water concentration rises

Change detected

Mechanism of action of ADH

Lumen of collecting duct

BloodCollecting duct cell

1. ADH

2. ADH receptor

3. Activation of protein kinase A

5. Fusion of vesicles containing AQP2 water channel proteins

H2O

4. Protein phosphorylation

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

BloodCollecting duct cell

ADH

ADH receptor

Protein kinase A

AQP2

Phosphorylated target proteins

Symptoms of diabetes insipidus

- Excessive thirst.

- Production of large quantities of dilute urine (‘insipidus’ = lacks flavour).

Overview of the action of ADH