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Introduction

The main purpose of cell signalling is to allow the activation or deactivation of genes which produce responses within the cell, generally so that they can respond to changes associated with the external or internal environment. For example, the increased uptake of glucose from the bloodstream stimulated by insulin or to activate cell division

Key Components

Before we begin, here are some terms which you should familiarise yourself with.

• Stimulus: a change in the external or internal environment
• Receptor: the cells or tissue which detects the changes
• Relay: the transmission of the message through nerves or hormones
• Effector: any part of the body that produces the response, e.g. gland secreting a hormone
• Response: the response that the effector carriers out
• Ligand: a signalling molecule

Stimulus Response Model

When a stimulus is detected by a receptor, a message is transmitted from the receptor to an effector which carries out a response.

Stimulus → Receptor → Signal Transduction → Effector → Response

Signal Receptors

The binding sites of receptors are very specific; they will only bind to specific ligands preventing them from reacting to every signal encountered by the cell

• Transmembrane receptors, these span the cell membrane and bind to hydrophilic ligands
• Intracellular receptors, these are located within the cell cytoplasm and bind to hydrophobic ligands

Signal Transduction

Signal transduction the conversion of an external stimulus into a response within the cell through the production of secondary messengers to amplify the signal

• Reception: the binding of the ligand to its specific receptor
• Signal Transduction: the conversion of the signal into a response e.g. a cascade is produced
• Cellular Response: the activation of cellular process within the cell

Hydrophobic Signalling Molecules

Because hydrophobic signalling molecules can diffuse across the plasma membrane, they have their specific receptors in the cytosol or the nucleus. When they bind to their receptor, they form a receptor-ligand complex which moves from the cytosol into the nucleus where it attaches to a specific region on a chromosome thereby activating or deactivating a specific gene and increasing or decreasing protein synthesis. Therefore, they directly regulate gene expression. Some examples of hydrophobic signalling molecules include testosterone, estrogen, progesterone, thyroxine, cortisol and retinoic acid.

Hydrophilic Signalling Molecules

Because hydrophilic signalling molecules are incapable of diffusing across the plasma membrane, they bind to specific transmembrane receptors and are regarded as being the first messenger. When they bind to their receptor, they catalyse the production of secondary messengers which then produces a cascade. This is allows for the amplification of the signal and relays it into the nucleus, where specific genes are activated and the response carried out. Some examples of hydrophilic signalling molecules include ADH, insulin, glucagon, adrenaline, oxytocin and neurotransmitters.

Modes of Transmission

There are three modes of transmission for signalling molecules that are required by the study design: autocrine, paracrine and endocrine.

• Autocrine: these act on the cell that produced it. This is important during development as once a cell is differentiated into a certain cell type; these signalling molecules reinforce further differentiation of the same cell (Cytokines)
• Paracrine: these are used to communicate locally by diffusing from their source to target cells nearby. Once the response is carried out, the signalling molecules are soon destroyed (Neurotransmitters, Cytokines)
• Endocrine: these travel a long distance via the bloodstream to distant target cells (Hormones, Cytokines)

Hormones

Hormones are chemical messengers which are secreted by endocrine glands and regulate the rate of existing activities, usually through the induction or repression of enzymes within distant target cells via the endocrine system. They travel in the bloodstream, having slower, but longer lasting effect and are effective in small quantities. Hormones which are amino acid derived or peptide/protein are hydrophilic, while lipid derived/steroid hormones are hydrophobic.

Neurotransmitters

Neurons use two types of signals

• Within a nerve cell by electrical signals. This is known as action potentials and transmits a nerve impulse along the axon of a neuron
• Between nerve cells using chemical signals that diffuse across the synaptic clefts (neurotransmitters)

When a neuron is stimulated, it transmits a nerve impulse in the form of an electrical signal along its axon; at the axon terminals are vesicles which contain neurotransmitters. The neurotransmitters are released by the impulse from the pre-synaptic neuron via exocytosis and travel across the synaptic cleft and bind with receptors on the surface of the post-synaptic neuron.

Neurotransmitters

Pheromones

Pheromones are chemical signals released by one member of a species and carried to another member of the same species into the outside environment. Once the pheromone is received, the body physiology and behaviour of the organism can be affected. Pheromones include, alarm, territorial, aggregation, trail and sex

Cytokines

Cytokines are signalling molecules that are secreted from a variety of cells of the immune system which allow them to communicate with each other. For example, interferon secreted from viral-infected cells signalling other cells to prevent the virus from entering

Necrosis

Necrosis is unplanned cell death which occurs when a cell is damaged by mechanical or chemical trauma thereby causing changes to the plasma membrane. This causes the cell to burst as the plasma membrane can no longer function effectively and the cell contents leak into the extracellular fluid

Apoptosis

Apoptosis is the systematic process that programs cell death in an orderly process. It plays a significant role in ensuring that a balance exists between cell production and cell loss. During apoptosis, special enzymes – lysozymes, package cell components into apoptotic bodies (blebs) which are engulfed by phagocytes. In apoptosis, cytokines produced by phagocytes protect surrounding cells by reducing inflammation and organelles may be recycled

• Cells which haven’t fully developed: e.g. when cells fail to be incorporated into the neural network in the brain of a developing embryo
• Excess cells, it costs energy and resources to maintain cells: e.g. some immune cells are produced in greater numbers than what is required
• Cells no longer needed: e.g. the cells between the digits which form the webbing, immune cells after the end of an infection

Mitochondria Pathway (Intrinsic)

When a cell is stressed by disease or serious damage, e.g. DNA damage or the malfunction of a crucial enzyme, proteins on the mitochondrial membrane are activated thereby disrupting the membrane and initiates a series of events. Pores open in the membrane of the mitochondria releasing Cytochrome C, activating caspases, enzymes which cleave DNA and protein.

Death Receptor Pathway (Extrinsic)

This is generally the pathway adopted for excess cells, old cells or those selected by the immune system. When ligands from outside the cell binds to the death receptor located on the plasma membrane, a cascade of reactions occurs, activating caspases which dismantle the cell.

Stages of Apoptosis

• Caspases cleave protein and DNA within the cell
• Cell shrinks, chromatin clumps and small blebs begin to develop
• The mitochondrion breaks down while the other organelles are usually left intact
• Cell fragments are packaged, forming apoptotic bodies
• Cytokines are secreted so normal cells nearby are left intact – reduce inflammation

Malfunctions of Apoptosis

• If apoptosis is inadequate: cells will live beyond their use by date and accumulate abnormally forming tumours
• If apoptosis is excessive: this can lead to disease as well. e.g. Parkinson’s and Alzheimer’s may be associated with an abnormal loss of nerve cells
• If apoptosis is inhibited: cells will continually divide uncontrollable due to mutations in the DNA causing cancer

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Additional Information:

Homeostasis

Homeostasis is the process that living organisms use to actively maintain a stable internal environment within narrow limits, while internal and external environmental conditions fluctuate

• Internal environment is the immediate surroundings of the cells including tissue fluid, blood and lymph
• Tissue fluid is in mammalian tissues where cells are surrounded by tiny channels and spaces filled with fluid
• Variables include temperature, blood pressure, glucose concentration, carbon dioxide concentration

Hormone Secretion

• Stimulated by a feedback mechanism – the level of glucose in the blood determines the secretion of insulin
• Stimulated by the nervous system – being scared mentally can induce the production of epinephrine
• Stimulated by another hormone – TSH stimulates the thyroid gland to produce thyroxine

Insulin

Insulin is secreted by the beta cells in the pancreas and regulates blood glucose levels. It forces many cells of the body to absorb and use glucose, thereby decreasing blood glucose levels. They are secreted in response to high blood glucose and inhibited by low blood glucose. Diabetes is caused by the deficient action of insulin while hypoglycaemia is caused due to excess action

Glucagon

Glucagon is secreted by the alpha cells in the pancreas and assists insulin in regulating blood glucose levels. It forces many cells of the body to release or produce glucose, thereby increasing blood glucose levels. They are secreted in response to low blood glucose and inhibited by high blood glucose. Sometimes nothing, but sometimes hypoglycaemia is caused by deficient action while hyperglycaemia is caused due to excess action

Auxin

• Auxin is a group of water-soluble hormones that are produced in the meristems of the apex in plants and are responsible in promoting cell elongation and expansion. However, they inhibit root growth when in high quantities
• In the cell wall, cellulose fibres are connected by cross bridges preventing the expansion of the cell. However, auxin causes the movement of hydrogen ions into the cell wall affecting the pH and then activates an enzyme which breaks the bridge, creating turgor pressure, thus, allowing water to enter and thus expanding the cell
• Auxins also play a part in phototropism, sunlight repels the auxin causing it to move towards the shaded part of the shoot, causing the plant to bend towards the sun as there is increased cell elongation on the shaded side
• Indole Acetic Acid is one of the most common auxins and is responsible for apical dominance. Apical dominance exists when lateral buds on the stem close to the apex of a plant are inhibited while the bud at the apex of a plant grows and develops. When the bud is removed, the source of IAA is removed, then lateral buds begin to develop

Cytokinins

• Cytokinins are plant hormones with the ability to stimulate cell division and differentiation – determining if a cell will form a root or shoot. Roots and developing fruits are the major sites of cytokinin synthesis due to the rapid rate of cell division
• They also help to suppress leaf ageing – senescence and increases yield
• High Cytokinin to Auxin ratio results in the production of new shoots
• Low Cytokinin to Auxin ratio results in the production of roots

Gibberellins

• Gibberellins are produced by roots, young leaves and seeds and exert their growth promoting effects mainly by causing elongation, but it can also stimulate cell division. (They can stimulate the growth of dwarf plants and fruit growth) They also initiate seed germination and bud growth
• When seeds germinate -> Gibberellin is produced by embryo -> Stimulates secretion of Alpha amylase and other enzymes -> These enzymes hydrolase the starchy endosperm -> Sugars and amino acids are produced -> Plants use this energy for germination and growth

Abscisic Acid

• Abscisic acid is produced in roots and terminal buds and assists plants to tolerate and avoid adverse conditions, e.g. drought, salinity and low temperatures, by promoting leaf drop, bud and seed dormancy and closing of the stomata

Ethylene

• Ethylene increases the rate of ripening by increasing the rate of respiration of cells in fruits and stimulates the breakdown of starches and oils into sugars. It is produced by ripening fruits and if a fruit is cut or damaged physically, then more ethylene would be produced and thus, the ripening process is accelerated
• It also causes abscission – the natural detachment of parts of a plant, typically dead leaves and ripe fruit