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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

Stimulus Response Model

 Cell Signaling

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

Back: Energy Transformations

 Next: Pathogens

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