Signalling Molecules and Signal Transduction

Signalling molecules The cells of an organism are constantly receiving information about their surrounding environment in order to control and regulate their activities. Cells also need to communicate to other cells to ensure the control and regulation of systems within the organism. Molecules that enable cells to receive information and communicate with other cells are called signalling molecules or ligands.

Receptors For a cell to act on and respond to a chemical signal the cell must have a receptor to receive the signal. Once the signalling molecule has interacted with the receptor, the information needs to be processed to produce the appropriate cellular response. Signal processing within a cell may involve a series of molecular steps called a signal transduction pathway.

Types of signals There is constant ‘chemical chatter’ between cells in multicellular organisms. Chemical signals can be classified according to the distance the signal needs to travel: –Autocrine signals – a cell secretes signalling molecules that can bind to its own receptors. –Paracrine signals – signals are released by cells into the extracellular medium in their neighborhood and act locally –Endocrine signals – signals produced in endocrine glands are secreted into the bloodstream and can be distributed throughout the body

Types of signals

Types of Signalling Molecules Hormones Neurotransmitters Pheromones Plant hormones

Hormones Production –Usually produced in endocrine glands. –Some neurons also produce hormones e.g. the neurons of the hypothalamus Transport –Travel in the general circulation (blood) or tissue fluid. Targets –Specific cells in the body respond to each hormone. –Target cells have a specific receptor for each hormone they respond to.

Types of hormones The chemical nature of a hormone influences the way it interacts with its target cells. Based on chemical structure hormones can be divided into three types. –steroid hormones –peptide hormones and protein hormones –amino acid derivatives

Steroid Hormones Are synthesised on demand from precursors in a cell. Leave the cell by simple diffusion. Have a long life span. Examples include: testosterone, oestrogen, progesterone and corticosteroids, all of which are synthesised from cholesterol.

Peptide/Protein hormones Peptide hormones ( 200 amino acids). Made in advance by a cell and stored in secretory vesicles. Leave the cell by exocytosis. Have a short life span. Examples of peptide/protein hormones include: adrenaline, thyroxine, oxytocin, antidiuretic hormone (ADH) and growth hormone

Amino acid derivative hormones Small molecules structurally related to a simple amino acid; for example, thyroid gland hormones are derived from tyrosine. Made in advance by a cell and stored, some in precursor form, in secretory vesicles until required. Leave the cell by exocytosis or, if a precursor, by simple diffusion. Have a short life span.

Key differences in hormones Steroid hormones –Have a lipid base, hence they are lipophilic and insoluble in water. –Require a carrier protein for transport by blood, which has a water base. –Lipophilic nature allows steroid hormones to pass through cell membranes that are phospholipid in nature. Amino acid hormones, peptide and protein hormones –Are water-soluble hormones and therefore hydrophilic. –Require no assistance to travel in the bloodstream. –Hydrophilic nature means they are unable to pass through phospholipid membranes without assistance. –Water-soluble hormones require the presence of a second messenger molecule, such as G protein, to transmit their message from the surface membrane receptor into the cytosol.

Signalling by hormones Lipid-soluble hormones pass through the cell membrane and bind to receptors in the cytosol. Water-soluble hormones bind to receptors in the cell membrane and stimulate second messenger systems. In both cases, the signals received by the cells go through a cascade of changes, called signal transduction, and finally the cell initiates its response.

Second messenger systems Receptors associated with second messenger systems include G protein-coupled receptors, tyrosine-kinase receptors, and ion-channel receptors. The ligand binds to a receptor on the cell's plasma membrane activating an associated molecule (the second messenger). The second messenger activates other intracellular molecules that elicit a response.

Second messenger systems

Neurotransmitters Most are peptides or modified amino acids Production –Produced in neurons and stored in synaptic vesicles Transport –Synaptic vesicles fuse with cell membrane following an electrical signal, and neutrotransmitters are released. The contents of the synaptic vesicles diffuse across the synaptic gap. Targets –Dendrites of another neuron in order to continue an impulse –Cells stimulated by neurons (muscles, glands)

Neurotransmittors A nerve ending in the region of a synapse with another cell, contains numerous mitochondria and many tiny vesicles containing neurotransmitter molecules. When an action potential enters the nerve ending, the vesicles move to the cell membranes and release their contents into the synaptic gap. These molecules diffuse across the gap to interact with specific receptors on the postsynaptic cell membrane.

Neurotransmitters Neurotransmitters cannot pass through the plasma membrane. They interact with a receptor on the cell surface which opens a protein channel and allows Na + (sodium ions) to enter the cell and change the membrane potential (important for electrochemical potential).

Pheromones May be simple modified hydrocarbons or more complex molecules Production –Produced in exocrine glands Transport –Molecules are secreted into the external environment. Targets –Other members of the same species. Animals of different species either don’t detect them or don’t respond to them.

Using pheromones against insect pests a)Normal zig-zag tracking of male moth along wafting stream of pheromone. b)The confusion strategy involves flooding an area with pheromone so that males become confused and cannot find female moths. c)Pheromone baits can lure moths into traps, reducing the size of the current population. d)A few baited traps can be used to monitor the size of a moth population in order to determine whether further action is required.

Plant Hormones Vary from simple organic molecules like ethylene to large complex organic molecules. Production –Produced by specialized cells in a variety of plant tissues. Transport –Generally by the plant’s vascular tissue –Ethylene is a gas and is able to diffuse through intercellular spaces. Targets –Cells which have receptors for the particular hormone. –One hormone can affect a variety of plant tissues.

Signal Transduction Signal transduction refers to the way that receptors on the cell surface convert incoming signals into information leading to an appropriately coordinated response. The binding of a signalling molecule with it specific receptor initiates a cellular response. Like homeostasis, the action of signalling molecules can be understood in terms of the stimulus response model. The binding of the signalling molecule to the receptor affects cellular chemicals. Changes in chemical activity in a cell cause changes in function.

SIGNAL TRANSDUCTION GROWTH SURVIVALPROLIFERATION SIGNAL DIFFERENTIATION MIGRATION APOTOSIS

Signal transduction cascades are the nervous system of the cell

The basics of signal transduction Signal is received. Signal is amplified. Response is usually a change in protein levels or associations. Specificity possible at all levels. Feedback possible. Conservation between many organisms... and pathways

Signal transduction amplifies the original signal The below-surface receptors activated by steroids and the G or other proteins activated as a result of water-soluble hormones both trigger a cascade of events. These events generally involve proteins and ultimately lead to a biological response within the cell relevant to the original hormone signal. This process in which a cell converts one kind of signal into another, by a series of relay molecules and other proteins, is called signal transduction. Within a cell, signal transduction amplifies the signal that the original hormone molecule brought to the cell. A signal brought by a single hormone molecule or a few hormone molecules can be amplified through many steps to induce reactions that involve many substrates.

Binding of antigen to a B cell receptor transduces a signal which upregulates transcription of genes important in proliferation of B cells. It can be seen that transduction of the signal is a non- linear process.

IMPORTANT CONCEPT: Signaling is nonlinear! Think of signal transduction as a web not a line...

Responses to Signals Activation of genetic material, DNA. May lead to the production of proteins, including enzymes. Enzymes become involved in a range of metabolic reactions within the cell. Response may be the production of another hormone that will leave the cell and carry different kinds of signals to other cells. Alternatively signals may suppress the production of proteins, including enzymes and therefore down-regulate particular metabolic reactions within the cell.

Apoptosis Apoptosis occurs in response to particular cell signals. Also known as programmed cell death (PCD), apoptosis is a normal part of the life of cells. Cell death is important for: –Developmental changes in growing embryos –Ridding tissues of old, infected or damaged cells –Removing immune cells which attack “self” –Removing cells which have sustained DNA damage so that they do not continue to reproduce and form cancers Too little apoptosis can lead to cancer and too much can cause degenerative diseases such as Alzheimer disease. Cell death occurs when the cell membrane shrinks, DNA fragments and lysosomes empty their contents into the cell causing the cellular components to be broken down. The dead cell is then consumed by phagocytes.