No man is an island entire of itself
John Donne1
Here, the 17th century English poet was referring to the necessary interconnectedness of people. Just like people, the 3.72 trillion cells that make up our bodies are also interconnected. In fact, multicellular organisms require cells to communicate with one another to coordinate one or many specialized functions. Everyday tasks such as digesting food, raising our hands, and reading this article, require coordination from various different types of cells. This process of cell communication is called cell signaling.
Importance of Cell Communication
Cell communication is critical for nearly every aspect of cell structure and cell function. Cell signaling can help explain how many cells work together to perform a function. For example, cell signaling is intricately tied to the regulation of cell growth, cell division, and cell energetics. Dysregulation of cell signaling may cause a cell to lose its ability to regulate cell division, leading to the formation of a malignant tumor and cancer. Therefore, the study of cell signaling is crucial for understanding the basis of human disease and, ultimately, human health.
Cancer is an outcome of dysregulated cell signaling. Typically when cells are damaged, there is a signal to initiate controlled cell death called apoptosis. However, the cell does not respond to these cell death signals in a cancer cell, leading to uncontrolled growth.
A cell that sends out a signal is called a signaling cell. The signal sent out by the signaling cell is called an extracellular signaling molecule or a ligand. The cell that receives the signal is called the target cell, and it contains proteins that bind to the ligand called receptors. Target cells can only respond to a signal if they express receptors that can bind to the ligand.
This diagram shows the basic components of cell communication.
A ligand or an extracellular signaling molecule is a chemical messenger that is released by the signaling cell.
A receptor is a protein that is expressed on the target cell that recognizes and binds to the ligand.
Types of Cell Communication
Imagine trying to communicate with someone sitting next to you in class. You could whisper, pass a note, or tap their shoulder to get their attention. How would your approach differ if you were trying to communicate with someone at another school? How about if you are trying to communicate with someone across the world?
The distance between you and the recipient changes how we communicate. If you were trying to communicate with yourself, you might make a mental note or write it down on your notetaking app. In contrast, if you were trying to communicate with someone across the world, you would have to look for alternative methods like the Internet.
Similarly, the distance that the signal travels between cells determines the mode of cell communication. In autocrine signaling, a cell communicates with itself. In paracrine signaling, a signaling cell communicates to nearby target cells. In endocrine signaling, a signaling cell releases a ligand that enters the bloodstream to bind distant target cells. Additionally, direct signaling occurs when cells are in direct contact communicate with each other.
Cell Communication Steps
Let's take a look at the steps in cell communication.
Cell Communication: Ligand-Receptor Binding
The first step of cell communication is when a ligand is released into the extracellular space by the signaling cell. Potential target cells can only respond to ligands if they have appropriate receptors that can bind the ligand. If compatible, the ligand will bind to the ligand-binding domain of the receptor, typically located on the extracellular or outer surface of the target cell. Once receptor-ligand binding occurs, it initiates a series of molecular processes within the cell called signal transduction that ultimately determine the cellular response of the target cell.
Study tip: Recall the cell membrane is the boundary of the cell that separates the outside environment (extracellular space) from inside the cell (intracellular space).
Cell Communication: Conformational Change in the Receptor
The second step of cell communication occurs following ligand-receptor binding when the receptor undergoes a conformational change (a change in shape) on its intracellular domain (just the part of the protein facing the inside of the cell) that activates nearby enzymes called effectors.
Effectors are enzymes that first interact with the intracellular domain of the receptor.
Effectors can then release small molecules called second messengers, which will travel around the cell activating or inhibiting different processes, causing the cell's response to the initial ligand.
One example is a class of receptors called G protein-coupled receptors (GPCRs). GPCRs are one class of receptors that have seven transmembrane domains and activate effectors called GTP-binding proteins following ligand binding. GPCRs are one of the most common membrane receptors, mediate a broad variety of physiological processes, and are involved in vision, taste, and smell.
Cell Communication: Signal Amplification via Second Messengers
Once the effector has been activated, the third step of cell communication begins. The effectors themselves can release small molecules called second messengers. Second messengers are responsible for relaying and amplifying the intracellular signal by activating proteins in the cell signaling pathway, such as protein kinases. Since one effector can release many second messengers, and those secondary messengers activate enzymes that target many proteins, thousands of proteins can be activated from a single effector. This process of recruiting more proteins to increase signal intensity is called signal amplification.
Cell Communication: Protein Activation by Phosphorylation
What does it mean when a protein is activated? At a molecular level, it means that a conformational change occurs in the protein leading to a change in its activity. Protein phosphorylation (or dephosphorylation) is the most common method by which a conformation change occurs, and hence a protein is activated. Protein phosphorylation is an addition of a phosphate functional group onto a specific amino acid residue of the protein.
Kinases are enzymes that catalyze the addition of a phosphate group onto proteins, while phosphatases are enzymes that catalyze the removal of phosphates in a process called dephosphorylation.
Importantly, whether phosphorylation leads to activation or deactivation is protein-specific and often also amino acid-specific.
Remember that structure and function are closely related in proteins, so a change in shape (a conformational change) will lead to a change in function (activation or deactivation).
Cellular Response
The second-to-last step of cell communication is a cellular response. Following signal amplification, the target cell needs to undergo a change to respond to the signaling cell. Depending on the cell and the ligand, the cell signaling response can range from:
- Changes in gene expression
- Rearrangements in the cytoskeleton
- Movement of the cell
- Cell growth or cell death
- Opening or closing of ion channels
- Release of chemical signals
Cell Communication: Signal Termination
The last step of cell communication is signal termination. It is critical that cells have tight regulation of cellular responses and can adapt to different environmental conditions; therefore, the signal needs to be terminated. One way to end cell signaling is to degrade the ligand by releasing extracellular enzymes. Alternatively, the receptor can be internalized, and both the ligand and receptor can be degraded.
Cell Communication Diagram
A cell communication diagram showing all the steps beginning at ligand-receptor binding and ending at its cellular response is shown below:
This diagram shows how cell communication typically occurs.
Cell Communication Examples
Examples of cell communication are prevalent in both nature and within our bodies. For example, harmful bacteria that enter our bodies contain proteins called antigens on their cell surface. Our immune cells contain receptors for these antigens (ligand), and if binding occurs, it leads to the destruction of these bacteria. This process is facilitated through direct cell-to-cell contact which exemplifies direct signaling.
While our focus has been on multicellular organisms, single-cell organisms also undergo cell communication. Quorum sensing is a process used by bacteria to control gene expression in response to their environment. When the concentration of bacteria is high in one area, bacteria release chemical ligands which act on themselves and other nearby bacteria to facilitate a behavioral change. Therefore, quorum sensing is a form of both autocrine and paracrine signaling.
Finally, hormones are a great example of endocrine signaling. When we have a meal, insulin released from the pancreas enters the bloodstream to reach skeletal muscle, liver, and adipose cells. Insulin then binds to insulin receptors which leads to the uptake of glucose into these target cells.
Cell Communication - Key takeaways
- Cell communication is important for determining cell function and structure in multicellular organisms.
- Dysregulation of cell communication can lead to cancer formation.
- The cell that releases the signal is called a signaling cell, while the cell that responds to the signal is called the target cell.
- Signaling cells release signals via chemical molecules called ligands.
- Only target cells with receptors that can bind to the ligand respond to the incoming signal.
- The three main types of cell communication are autocrine, paracrine, and endocrine signaling. Direct signaling is a subtype of paracrine signaling.
- The steps in signal transduction are ligand-receptor binding, conformation change of the receptor, signal amplification, cellular response, and signal termination.
1. John Donne, No Man is an Island, 1624
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