Cellular Response

Cellular Signaling Steps: Signal reception, signal transduction, and cellular response

Cells respond to signals from its environment through a process called cell signaling, in which a signaling molecule called ligand binds to a receptor protein, initiating a specific cellular response.

The process of cell signaling can be summarized in three basic steps:

1. Signal reception in which the ligand binds to the receptor protein.

2. Signal transduction in which the signal that was transmitted by the binding of the ligand to the receptor is relayed through the activation of molecules, one after another, in a signaling pathway. This step takes place when a ligand binds to a cell-surface receptor.

3. Cellular response in which the signal ultimately initiates a specific cellular process.

Cellular response definition

Cellular response can be defined as the final step of the cell signaling process in which a specific function or process such as cell division is initiated in the cell’s nucleus or cytoplasm.

Many signaling pathways ultimately regulate the synthesis of proteins by turning certain genes in the nucleus “on” or “off."

• The final molecule in some pathways can function as a transcription factor that activates genes and initiates transcription.

• In other pathways, the final molecule can function as a transcription factor that inactivates genes and inhibits transcription.

Other pathways regulate the activity of proteins rather than initiating or inhibiting their synthesis. These pathways typically affect proteins that perform their functions in the cytoplasm outside the nucleus.

Cellular response diagram

Figure 1 below shows cellular response as the final step of the cell signaling process.

Cellular response regulation

There are many ways by which the extent and specificity of the response are regulated. In this section, we’ll discuss four ways: signal amplification, signal specificity and response coordination, signaling efficiency, and termination of the signal.

Signal amplification

In a signaling pathway, enzyme cascades amplify the cell’s response to a signaling event. With each step in the cascade, the number of activated molecules becomes increasingly greater. This is because these proteins are active long enough to digest numerous molecules of substrate before becoming inactive again.

Signal specificity and response coordination

Cells respond to signals differently. Let’s take a liver cell and a heart muscle cell as an example. Both of these are in contact with the bloodstream, so they are both exposed to various hormone molecules and local regulators secreted by adjacent cells.

However, the liver cell might respond to a signal that the heart cell might ignore, and vice versa. Moreover, some signals can trigger responses in both cell types, albeit differently.

This is because different types of cells activate different sets of genes and proteins. A cell's reaction to a signal is determined by the type of signal receptor proteins, relay proteins, and proteins that it has that will carry out the response.

Signaling efficiency

For some signaling pathways, the presence of scaffolding proteins increases the efficiency of signal transduction. Scaffolding proteins are large relay proteins with other relay proteins attached. In some cases, scaffolding proteins themselves may activate relay proteins.

Signal termination

Molecular changes in a signaling pathway must take place quickly enough so that the cell is able to respond to incoming signals. When the concentration of ligands decreases, more receptors are free to revert to their inactive form.

A cellular response only takes place when the concentration of ligand-bound receptors is above a certain threshold. Below this threshold, the cellular response stops.

In turn, relay molecules return to their inactive state in their specific ways: for example, cAMP is converted to AMP by the enzyme phosphodiesterase. With this, the cell is once again ready to respond to a new signal.

Cellular response examples

Now that we have discussed what cellular response is and how it is regulated in cell signaling, we can move on to some pertinent examples. Here we will discuss apoptosis and immune response.

Apoptosis or programmed cell death

When cells are infected, damaged, or near the end of their functional lifespan, they might undergo apoptosis or "programmed cell death”.

In apoptosis, the DNA is broken up, while organelles and other cytoplasmic components are fragmented. The cell then shrinks and becomes lobed, a process called “blebbing”. The cell's components are then bundled into vesicles, which are devoured and consumed by specialized phagocytes, leaving no trace. Apoptosis protects nearby cells from the damage that would occur if a dying cell just poured out all of its contents.

Apoptosis can be triggered by a signal originating from outside or within the cell.

• When an external signaling molecule binds to a cell-surface receptor, enzymes called caspases which cleave specific proteins in the nucleus and cytoplasm are activated. Caspases alongside other enzymes carry out apoptosis.

• Within the cell, the signal that leads to apoptosis can come from the nucleus when DNA suffers considerable damage or the endoplasmic reticulum when there is excessive protein misfolding.

Cell death occurs for many different reasons. Some are more straightforward: for example, cell death during the embryonic development of mice leads to the formation of individual fingers from what was initially a spade-like structure.

Another reason for cell death could be that the tissue is no longer needed by the organism: for instance, when a tadpole develops into a frog, its tail cells undergo apoptosis, causing the tail to disappear.

Apoptosis also helps regulate cell growth in adult tissues. Without such balance, the tissue would expand or contract. Let’s say a portion of an adult rat’s liver is removed: the liver cells grow to compensate for the loss. Now let’s say the same rat liver is treated with the drug phenobarbital which stimulates cell growth in the liver and eventually causes the liver to become enlarged.

When the treatment is stopped, the rate of apoptosis increases until the liver has shrunk back to its previous size. This example shows how the regulation of both cell death and cell growth rate keeps organs like the liver at a constant size.

Immune system cellular response

How do immune system cells called T cells enable the body’s immune system response? While this mechanism is not fully understood, researchers hypothesized that when a receptor on a T cell recognizes an antigen such as a viral protein, it triggers an immune response.

First, the T cell receptor undergoes conformational changes starting from the antigen recognition site located outside the cell to a signaling site within the cell.

Then, a signaling cascade is triggered within the T cell, triggering varying cellular responses, including the recruitment of other immune cells, the proliferation, and differentiation of T cells, or the killing of infected or cancerous cells.