(a) Co-ordination

• 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

• Binding changes the conformation of the receptor, which initiates a response within the cell

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

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

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

(b) Hydrophobic signals and control of transcription

• 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

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

• 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

  • The hormone-receptor complex binds to specific DNA sequences called hormone response elements (HREs). 

  • Binding at these sites influences the rate of transcription, with each steroid hormone affecting the gene expression of many different genes.

(c) Hydrophilic signals and transduction

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

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

• 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

• 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

  • G-proteins relay signals from activated receptors (receptors that have bound a signalling molecule) to target proteins such as enzymes and ion channels. (Details of G-proteins subunits are not required).

• 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.

• 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.

• Diabetes mellitus can be caused by failure to produce insulin (type 1) or loss of receptor function (type 2)

• Type 2 is generally associated with obesity

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

(d) Nerve impulse transmission

(i) Generation of a nerve impulse

• 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

• 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

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

  • Ion movement occurs and there is depolarisation of the 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.

• 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

• 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.

(ii) Initiation of a nerve impulse in response to an environmental stimulus: the vertebrate eye

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

  • Rods function in dim light but do not allow colour perception. Cones are responsible for colour vision and only function in bright light.

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

• In rod cells the retinal-opsin complex is called rhodopsin

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

• A cascade of proteins amplifies the signal

• Photoexcited rhodopsin activates a G-protein, called transducin, which activates the enzyme phosphodiesterase (PDE)

  • A single photoexcited rhodopsin activates hundreds of molecules of G-protein. Each activated G-protein activates one molecule of PDE.

• PDE catalyses the hydrolysis of a molecule called cyclic GMP (cGMP)

  • Each active PDE molecule breaks down thousands of cGMP molecules per second. 

  • The reduction in cGMP concentration as a result of its hydrolysis affects the function of ion channels in the membrane of rod cells.

• This results in the closure of ion channels in the membrane of the rod cells, which 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