Signal Transduction

Signal transduction pathway

During signal transduction, a cell releases signals. These signals can be in the form of a chemical ligand such as a neurotransmitter, hormone, or molecule.¹

Cell communication can occur over short distances. Neurotransmitters allow signals to travel across the synaptic cleft into the neighbouring neuron to initiate changes.¹ Similarly, gap junctions that join neighbouring cells together allow small signalling molecules like Na⁺ to flow directly between cells. But cell communication can also occur over long distances.¹ This is accomplished through the use of hormones. Hormones released from endocrine glands such as your adrenal glands travel to target cells via your bloodstream.¹ Usually, the target cells of your endocrine system are located in multiple organ systems. So how does a ligand know when it has reached its target? This is done via receptors!

Signal transduction pathway steps

Almost all cell communication pathways have three stages: reception, signal transduction, and cellular response.¹ During a typical cell communication pathway, the signalling cell releases its signal into the extracellular matrix. Once in the matrix, a signal travels to the target cell. Target cells are loaded with receptors on their surfaces and/or in their cytosol. There are many different types of receptors in the human body each with their own ligands. For example, dopamine receptors like AMPA receptors only bind to dopamine and cause the target cells to take in more Na⁺ ions.

Signal transducing receptors are classified into four main classes:³

1. Enzyme-linked receptors

   • These are receptors that extend through the target cell's plasma membrane and can function as an enzyme or work to activate or produce enzymes.³

2. G-protein coupled receptors

   • These receptors are bound to G proteins inside the cell.³

3. Nuclear receptors

   • Receptors that are located inside the nucleus and function to alter gene expression within the target cell.³

4. Ligand-gated ion channels

   • These receptors are ion channels that open or close when their ligand is bound to them. These receptors are located on the target cell's plasma membrane.

When your body responds to stimuli or an invading pathogen, certain classes of receptors are activated when certain ligands are released. Once activated, these receptors will initiate necessary functions to bring the body back to homeostasis (to its original state of equilibrium) or to allow your body to do a specific function. Activated receptors work in different ways depending on their class. For example, internal receptors travel to the nucleus to alter gene expression in the target cell.³ A change in gene expression may cause the target cell to die, produce another signal, or become another cell (in the case of stem cells).

Likewise, membrane receptors such as ligand-gated ion channels work by opening and closing to allow certain ions like Na⁺ or K⁺ to enter and leave the cell.³ Similarly, G-protein coupled receptors cause many reactions inside the cell to produce different cell responses. Disruptions in signal transduction are associated with many diseases.³

It is important to recognize that each cell in your body has many different receptors, allowing them to respond to various ligands and stimuli. Some receptors are capable of binding to multiple different ligands; for example, pain receptors bind both pain neurotransmitters and ligands found in pain medication. The capacity of receptors to bind to different ligands is the basis of modern medicine. It allows diseases and conditions to be treated with pharmaceuticals.

Types of signal transduction

Once a ligand binds to a receptor, a series of events need to take place in order for the target cell to produce a cellular response. These events are known as signal transduction. Signal transduction only takes place with membrane receptors like ligand-gated ion channels and G-protein coupled receptors since internal receptors are able to interact directly with the target cell's DNA.³ When a ligand binds to its membrane receptor, conformational changes occur that affect the receptor's intracellular domain.

There are many different types of signal transduction pathways that play different roles in mediating cellular responses. Let’s discuss a few of these pathways below.

Akt signalling pathway

The Akt signalling pathway is known as the pro-survival pathway. It plays major roles in protein synthesis, metabolism, cell proliferation, and the cell cycle.² This signal transduction pathway happens multiple times a day as your body replenishes dying cells, metabolizes food, and creates new proteins for various bodily functions.² The Akt pathway is an essential component of homeostasis. Fig. 2 depicts the entire Akt pathway that your cells undergo to maintain your body. This pathway may seem daunting at first but we will walk through it to ensure your understanding. Let’s start at the receptor level. Ligands such as growth factors and cytokines bind to membrane receptors on the cell’s surface which activates protein kinase 3 (PI3K). The activation of protein kinase 3 initiates the AKT pathway.

The activation of PI3K causes the conversion of phosphatidylinositol-bisphosphate (PIP2) to phosphatidylinositol trisphosphate (PIP3).² PKB/Akt binds to PIP3 at the plasma membrane, allowing PDK1 to access and phosphorylate AKT.² This Akt modification is sufficient to activate mTORC2 which directly phosphorylates AKT causing the inhibition of tuberous sclerosis protein 2 (TSC2). Rheb then forms a complex with GDP which is phosphorylated into GTP.² Together, Rheb and CTP activate the transcription factor mTORC1. The activation of mTORC1 alters the cell's gene expression in order to promote cell growth, survival, and other helpful mechanisms.²

You will likely not be tested on the entire pathway, but it is good to review each step to understand how many components are needed for successful signal transduction.

AMPK signalling pathway

Another important pathway is the AMPK signalling pathway. This signalling pathway is activated in response to low levels of energy (ATP). Reduced levels of available ATP are caused by stress, low oxygen (hypoxia), heat shock, or other conditions where homeostasis is heavily interrupted.² The AMPK pathway is responsible for activating enzymes that restore cellular levels of available ATP.² This prevents affected cells from dying due to a lack of nutrients. The AMPK pathway acts as a temporary fix to low ATP levels. If the body is not stabilized in a timely manner, your cells will die.²

Apoptosis pathway

Apoptosis is programmed cell death and is essential for maintaining homeostasis.² You may be wondering why your body has self-destruction protocols in its hardware. Well, apoptosis allows for the replenishment of old worn-out cells with new healthy cells.² The reason why your cells self-destruct is that dying cells cause widespread inflammation in the body by releasing inflammatory cytokines.

Dying cells initiate the apoptosis pathway within themselves. This means that dying cells respond to their own signals. Once the self-destruct signal is released, receptors on the dying cells surface.

Signal transduction in plants

An important part of plant physiology is the ability to undergo photosynthesis. Photosynthesis is a crucial process for a plant's survival. The way you think about photosynthesis may be extremely broad. I’m school we learn that plants harness energy from the sun to create energy for their cells. But how exactly do these plants gather energy? The answer is signal transduction! Like animal cells, plant cells also carry out complex signalling pathways in order to maintain homeostasis. Let's look at the potato plant as an example.

As a potato plant initially develops underground, it is growing in the absence of light a process known as etiolation.⁴ Etiolation is a powerful process because a developing potato plant has no green pigment and therefore cannot carry out photosynthesis. As the potato plant emerges above ground and is exposed to sunlight, the plant begins to develop green pigment on its leaves.⁴ The process of developing green pigment is called de-etiolation.⁴ So how does de-etiolation occur?

As the potato plant emerges, sunlight stimulates a phytochrome receptor found in the plant cell's cytosol.⁴ The signal is then transduced via cyclic GMP; a second messenger that activates protein kinase.⁴ Meanwhile, light signals also activate calcium channels on the plant cell's membrane allowing calcium to rush into the cell to activate another protein kinase.⁴ The activation of these two kinases leads to the phosphorylation of transcription factors which alters the plant's gene expression and causes it to turn green by developing proteins necessary for carrying-out photosynthesis.⁴ Figure 3 depicts the process of de-etiolation.