KA 1.4 Communication and Signalling

Multicellular Organisms and Cellular Communication

Communication in Multicellular Organism

• Multicellular organisms show division of labour, this means that different cells carry out different functions within defined areas of the body.

• The cells of the body must be able to communicate with each other.

• They must be able to receive information from other parts of the body and act upon it.

• Multicellular organisms signal between cells using extracellular signalling molecules.

• Steroid hormones, peptide hormones, and neurotransmitters are examples of extracellular signalling molecules.

• Receptor molecules of target cells are proteins with a binding site for a specific signal molecule.

Signal Transduction Pathway

• When an extracellular signalling molecule (such as a hormone) binds to and activates a specific receptor, signal transduction occurs.

• The receptor may be located on the surface of the cell or inside the cell.

• Reception triggers a series of events inside the cell, resulting in a response, e.g. activation of an enzyme or G-protein, or the activation of proteins that regulate gene transcription.

• Signalling molecules may have different effects on different target cell types due to differences in the intracellular signalling molecules and pathways that are involved.

Tissue-Specific Response

• Receptor molecules of target cells are proteins with a binding site for a signal molecule.

• Binding changes the conformation of the receptor and this can alter the response of the cell.

• Different cell types produce specific signals which can only be detected and responded to by cells with the specific receptor.

• In a multicellular organism, different cell types may show a tissue-specific response to the same signal.

Hydrophobic Cell Signals

Hydrophobic Signals

• Hydrophobic signalling molecules can diffuse directly through the phospholipid bilayers of membranes, and so bind to intracellular receptors

• The receptors for hydrophobic signalling molecules are transcription factors.

• Hydrophobic signalling molecules are able to do this because the tails of the phospholipids in the plasma membrane are also hydrophobic and allow the molecules to pass across.

• Transcription factors are proteins that when bound to DNA can either stimulate or inhibit initiation of transcription.

Transcription Factors

• The receptor proteins for steroid hormones are transcription factors.

• A transcription factor is a protein which binds to DNA and controls the rate of transcription.

• Transcription factors can enhance or block the binding of RNA polymerase to specific genes, thereby controlling whether the gene is transcribed or not.

Steroid Hormones

• The steroid hormones oestrogen and testosterone are examples of hydrophobic signalling molecules.

• Steroid hormones bind to specific receptors in the cytosol or the nucleus.

• The hormone-receptor complex moves to the nucleus where it binds to specific sites on DNA and affects gene expression.

• Steroid Hormone passes across plasma membrane

• The hormone binds to the receptor protein, activating it

• The hormone-receptor complex binds to specific DNA sequences called Hormone Response Elements (HREs)

• Binding at Hormone Response Elements influences the rate of transcription with each steroid hormone affecting the gene expression of many genes.

Thyroxine

• Thyroxine is a hydrophobic hormone produced by the thyroid gland.

• It is involved in regulating the rate of metabolism.

• It is hydrophobic, it can cross the plasma membrane of a cell and interact with proteins inside the cell.

• When thyroxine is not present, its receptor protein binds onto the DNA in the nucleus.

• This inhibits the transcription of the gene for Na/K-ATPase (sodium-potassium pump).

• When thyroxine is present, the receptor protein undergoes a conformational change and can no longer bind the DNA.

• This allows transcription of the gene for Na/K-ATPase (sodium-potassium pump) to take place.

• Increased production of the Na/K-ATPase (sodium-potassium pump) results in an increase in metabolic rate.

Hydrophilic Cell Signals

Hydrophilic Signalling

• Hydrophilic signalling molecules bind to transmembrane receptors and do not enter the cytosol.

• Transmembrane receptors change conformation when the ligand binds to the extracellular face.

• The signal molecule does not enter the cell, but the signal is transduced across the plasma membrane.

• Peptide hormones and neurotransmitters are examples of hydrophilic extracellular signalling molecules.

Hydrophilic Signals

• Hydrophilic signalling molecules include peptide hormones and neurotransmitters.

• Hydrophilic signals require receptor molecules to be at the surface of the cell because they are not capable of passing across the hydrophobic plasma membrane.

Hydrophobic Signalling Molecules

Stage 1 - Reception

1. Transmembrane receptors change conformation (shape) when the ligand (signalling molecule) binds outside the cell.
2. The signal molecule does not enter the cell, but the signal is transduced across the membrane of the cell.

Stage 2 - Transduction

• Transmembrane receptors act as signal transducers by converting the extracellular ligand-binding event into intracellular signals, which alters the behaviour of the cell.

• Transduced hydrophilic signals often involve G-proteins or cascades of phosphorylation by kinase enzymes.

Kinase Enzymes

• Phosphorylation can either activate a protein (top) or inactivate it (bottom).

• Kinase is an enzyme that phosphorylates proteins.

• Phosphatase is an enzyme that dephosphorylates proteins, effectively undoing the action of kinase.

Transduction by G-Proteins

• G-protein-coupled receptors (GPCRs) are linked to a G-protein.

• The G-protein acts as a switch that is either on or off, depending on which of the two guanine nucleotides (GDP or GTP) is attached.

• G-proteins relay signals from activated receptors (receptors that have bound a signalling molecule) to target proteins such as enzymes and ion channels.

• When a hydrophilic signalling molecule binds to the extracellular side of a GPCR, a cascade of events is initiated.

Transduction by Phosphorylation

• Phosphorylation cascades allow more than one intracellular signalling pathway to be activated.

• Phosphorylation cascades involve a series of events with one kinase activating the next in the sequence and so on.

• Phosphorylation cascades can result in the phosphorylation of many proteins as a result of the original signalling event.

• Kinase enzymes carry out# phosphorylation reactions (addition of a phosphate group to substrates).

Insulin

• The levels of glucose in the blood must be kept within strict limits.

• Hormones are involved in maintaining a constant blood glucose level.

• An increase in blood glucose concentration is detected by cells in the pancreas, which produce insulin.

• Insulin plays an important role in allowing fat tissue and skeletal muscles to absorb glucose from the bloodstream.

• Glucose passes into cells by travelling through transporter proteins in the plasma membrane (by facilitated diffusion).

• Binding of the peptide hormone insulin to its receptor results in an intracellular signalling cascade that triggers recruitment of GLUT4 glucose transporter proteins to the cell membrane of fat and muscle cells.

• Binding of insulin to its receptor causes a conformational change that triggers phosphorylation of the receptor. This starts a phosphorylation cascade inside the cell, which eventually leads to GLUT4-containing vesicles being transported to the cell membrane.

• GLUT4 transporters allow glucose to pass across the plasma and enter the cell though facilitated diffusion.

Diabetes Mellitus

• In some individuals, there is a failure at some stage of the insulin signalling pathway. This results in a condition called diabetes.
• There are two type of diabetes:
  • Type 1 - caused by a failure to produce insulin in the pancreas.
  • Type 2 - caused by loss of
    insulin receptor function. This
    type of diabetes is usually
    associated with obesity.

Diabetes Treatment

• Type 1 diabetes is treated with regular injections of insulin throughout the day and a healthy diet.

• Type 2 diabetes may be treated with medications to lower blood glucose levels along with lifestyle changes, which may include consuming less sugar and increasing activity levels (this will aid weight loss if this is necessary).

• Exercise also triggers recruitment of GLUT4 so can improve uptake of glucose to fat and muscle cells in subjects with Type 2 diabetes.

Ion Channels and Nerve Transmission

Electrical Potential Difference

• All cells have an electrical potential difference (voltage) across their plasma membrane.

• This voltage is called the membrane potential. In neurons, the membrane potential is typically between -60 and -80mV (millivolts) when the cell is not transmitting signals.

• The minus sign means that the inside of the cell is negative relative to the outside.

Membrane Potential

• Resting membrane potential is a state where there is no net flow of ions across the membrane.

• The transmission of a nerve impulse requires changes in the membrane potential of the neuron’s plasma membrane.

• An action potential is a wave of electrical excitation along a neuron’s plasma membrane.

Nerve Transmission

• The resting potential is generated and maintained by the action of the sodium-potassium pump, removing three positively charged sodium ions from the cell and only allowing two positively charged potassium ions into the cell.

• Nerve transmission is a wave of depolarisation of the resting potential of a neuron.

• Depolarisation - an electrical state in an excitable cell whereby the inside of the cell is made less negative relative to the outside than at the resting membrane potential.

• This can be stimulated when an appropriate signal molecule, such as a neurotransmitter, triggers the opening of ligand-gated ion channels at a synapse.

• When a ligand-gated ion channel opens in response to a neurotransmitter, it may trigger depolarisation.

• This means the resting potential of the membrane increases. If the change is big enough it may trigger an action potential (a signal that carries information along axons).

Neurotransmitters

• Neurotransmitters initiate a response by binding to their receptors at a synapse.

• Neurotransmitter receptors are ligand-gated ion channels.

• Depolarisation of the plasma membrane as a result of the entry of positive ions triggers the opening of voltage-gated sodium channels, and further depolarisation occurs.

• Depolarisation is a change in the membrane potential to a less negative value inside.

• Inactivation of the sodium channels and the opening of potassium channels restores the resting membrane potential.

Ion Movement at a Synapse

• Binding of a neurotransmitter triggers the opening of ligand-gated ion channels at a synapse.

• Ion movement occurs and there is depolarisation of he plasma membrane.

• If sufficient ion movement occurs, and the membrane is depolarised beyond a threshold value, the opening of voltage-gated sodium channels is triggered and sodium ions enter the cell down their electrochemical gradient.

• This leads to a rapid and large change in the membrane potential.

• A short time after opening, the sodium channels become inactivated.

• Voltage-gated potassium channels then open to allow potassium ions to move out of the cell to restore the resting membrane potential

Spread of Depolarisation

• Depolarisation of a patch of membrane causes neighbouring regions of membrane to depolarise and go through the same cycle, as adjacent voltage-gated sodium channels are opened.

• When the action potential reaches the end of the neuron it causes vesicles containing neurotransmitter to fuse with the membrane this releases neurotransmitter, which stimulates a response in a connecting cell.

Repolarisation

• Restoration of the resting membrane potential allows the inactive voltage-gated sodium channels to return to a conformation that allows them to open again in response to depolarisation of the membrane.

• Ion concentration gradients are re-established by the sodium-potassium pump, which actively transports excess ions in and out of the cell.

• Following repolarisation the sodium and potassium ion concentration gradients are reduced.

• The sodium-potassium pump restores the sodium and potassium ions back to resting potential levels.

Nerve Transmission (Summarised Steps)

1. Binding of a neurotransmitter triggers the opening of ligand-gated ion channels at a synapse.
2. Ion movement occurs and there is depolarisation of the plasma membrane.
3. If sufficient ion movement occurs, and the membrane is depolarised beyond a threshold value, the opening of voltage-gated sodium channels is triggered and sodium ions enter the cell down their electrochemical gradient.
4. This leads to a rapid and large change in the membrane potential.
5. A short time after opening, the sodium channels become inactivated.
6. Voltage-gated potassium channels then open to allow potassium ions to move out of the cell to restore the resting membrane potential.
7. Ion concentration gradients are re-established by the sodium-potassium pump, which actively transports excess ions in and out of the cell.

Detecting and Amplifying an Environmental Stimulus

Photoreceptor Proteins in Animals

• The retina is the area within the eye that detects light and contains two types of photoreceptor cells: rods and cones.

Rods and Cells

• Animals have two types of photoreceptor cells within the retina of the eye:
  • 125 Million Rods
  • 6 Million Cones

Rod Cells

• Rod cells contain one type of light-sensitive pigment.

• Rods function in dim light but do not allow colour perception.

• These cells are sensitive to changes in light intensity and are particularly useful for vision in areas of low light intensity, e.g. a dim room.

• Nocturnal animals have a greater proportion of rod cells in their retina which gives them better vision at night.

Cone Cells

• Cones are responsible for colour vision and only function in bright light.

• Cone cells are particularly sensitive to specific colours (wavelengths) of light

  • green, red, blue and (in some animals) UV.

• Cone cells allow animals to have colour vision.

• People who are colour blind lack a particular type of cone cell in their retina.

Photoreceptor Proteins in Animals

• In animals the light-sensitive molecule retinal is combined with a membrane protein opsin to form the photoreceptors of the eye.

• A cascade of proteins amplifies the signal.

Retinal

• Each rod or cone cell in the retina contains visual pigments that consist of a light-absorbing molecule, called retinal.

• Retinal is bonded to a membrane protein, called opsin.

• In combination, opsin and retinal make up the visual pigment rhodopsin.

• Retinal absorbs a photon of light and rhodopsin changes conformation to photoexcited rhodopsin.

Rhodopsin Activation

Generation of a nerve impulse is brought about when:

1. Retinal absorbs a photon of light and rhodopsin changes conformation to photoexcited rhodopsin.
2. Photoexcited rhodopsin activates a G-protein called transducin.
3. Transducin activates the enzyme phosphodiesterase (PDE)
4. PDE catalyses the hydrolysis of a molecule called cyclic GMP (cGMP)
5. The reduction in cGMP concentration as a result of its hydrolysis causes the
   closure of ion channels in the membrane of the rod cells.
6. The inward leakage of positive ions (Na+ and Ca+) is halted so the membrane potential increases; hyperpolarisation (more negative charge) triggers nerve impulses in neurons in the retina.

• A very high degree of amplification results in rod cells being able to respond to low intensities of light.

• In cone cells, different forms of opsin combine with retinal to give different photoreceptor proteins, each with a maximal sensitivity to specific wavelengths: red, green, blue or UV.

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