Cell Signaling and Regulation - An Overview

Introduction

The growth of the cells and other cellular activities performed by them are regulated by signals transmitted by the neurotransmitters, growth factors, hormones, and extracellular matrix components. The human body has a network of nerves called the nervous system that controls every organ, tissue, and cell. The nerve cells send and receive signals from all over the body. This cell signaling is essential for the body to function properly.

What Is Cell Signaling?

Cell signaling is a combination of biological and chemical processes that gives responses to the environment and the body. When a ligand (a molecule that binds to the receptor protein) binds to the receptor, it induces certain biochemical changes by modifying the body's genetic expressions, cytoskeletal arrangements, or metabolism. The normal cell processes are regulated with the help of cell signals. But if there is any alteration in the cell signaling, it can result in numerous disorders and diseases like cancer.

What Are the Kind of Signals Received by the Cells?

Neurotransmitters are messengers that carry chemical messages or signals from one nerve cell or neuron to the target cell, like a nerve cell, gland, or muscle cell. Some cells, like sensory cells in the skin, respond to mechanical stimuli like pressure from the touch.

What Are the Functions of Neurotransmitters?

The neurotransmitters help in controlling many body functions like -

• Breathing.

• The movement of the muscles.

• Heartbeat.

• The pressure variation of the blood vessels.

• Hormonal regulation.

• Digestion.

• Maintainance of appetite and thirst.

• Five senses like touch, feel, seeing, hearing, and taste.

• Sleep cycle.

• Healing.

• Thoughts and memories.

How Are the Signals Recognised by the Cells?

The cells recognize the signal with the help of a transmembrane protein called receptors. The receptors will bind with signaling molecules and produce a physiological response. Each molecule has a specific receptor. For example, dopamine will only bind with dopamine receptors, nerve growth factor only binds with nerve growth factor rector, insulin with the insulin receptors, etc. Cellular receptors are of different types and can be categorized into five classes -

• Internal Receptors - Internal receptors are also called cytoplasmic or intracellular receptors. They are called cytoplasmic receptors because they are present in the cell's cytoplasm. They have hydrophobic ligands.

• Cell Surface Receptors - These are called transmembrane receptors. These transmembrane proteins are seen on the surface of cells and the plasma membrane. They have hydrophilic ligands.

• Ion Channel Receptors - Ion channel receptors allow specific ions to pass through the plasma membrane. When the ligand (a molecule that binds to the protein or the receptor) binds with the receptor, there is a change in the shape of the receptor through which specific ions like sodium (Na), magnesium (Mg), hydrogen (H+), or calcium (Ca++).

• G-Protein-Coupled Receptors - It is a type of cell surface receptor. It acts through G-protein, which creates a second messenger cascade. The ligand binding site of G-protein coupled receptors is present on the outer surface of the plasma membrane. It has a transmembrane part that allows the transfer of signals to intracellular space to bind to G-protein coupled receptors.

• Enzyme-Linked Receptors - Enzyme-linked receptors have catalytic sites present on the cytoplasmic membrane. When the ligand binds with the enzyme-linked receptor in the catalytic site, enzymatic activity results. Tyrosine kinase receptors are the most common type of enzyme-linked receptors.

What Is Protein Phosphorylation?

It is a reversible mechanism in which phosphate is changed to amino acids with the help of the enzyme protein kinases. The most common phosphorylation events are serine (non-essential amino acid) and threonine (an amino acid used to produce proteins) phosphorylation. Protein phosphorylation can help in cell signaling. The factors that influence phosphorylation-dependent signaling are -

• The control of phenotypes or traits by the signaling networks.

• The cellular difference in the signaling process.

• Depends on the environment.

How Do the Cells Respond to the Signals Received?

When a ligand binds to the receptor, there is a formation of a chemical signal and biochemical reactions. This pathway is called signal transduction cascade. The chemical and physical signal received is transmitted by a series of events like protein phosphorylation which is usually catalyzed by protein kinases. These events result in the cellular response.

When activated, the receptors can synthesize second messengers, which control the intracellular signaling pathways. An example of a second messenger is cyclic adenosine monophosphate or cyclic AMP (cAMP). Adenosine triphosphate (ATP) synthesizes cyclic AMP with the help of the enzyme adenylyl cyclase. Thus, when the adenylyl cyclase is activated, a higher amount of cyclic AMP molecules will be produced. A large production of cyclic AMP molecules activates the protein kinase A (PKA) enzyme, resulting in phosphorylation (attaching a phosphate group to a molecule). The enzyme phosphodiesterase can stop the signals produced by cyclic AMP.

How Are the Signals Affecting the Cell Function?

The transfer of the phosphate group from adenosine triphosphate (ATP) molecules to protein molecules is catalyzed by the enzymes such as protein kinase A and protein kinase C. In the intracellular signaling pathway, the activity of enzymes is controlled by the phosphorylation reaction. Phosphate groups can induce changes in the enzymes, activating or inhibiting the enzymatic activity. Hence, the effect of enzyme activity can be reversed by removing the phosphate groups.

How Is the Cell Signaling Process Measured That is Involved in the Protein Phosphorylation?

Protein phosphorylation can be measured to determine the cell signaling process. The methods of measuring the cell signaling process are -

• Western Blotting - It uses an electrophoretic separation technique. It separates deoxyribonucleic acid, ribonucleic acid, or protein based on their electrical charges and size.

• Fluorescence Microscopy - Uses fluorescence for measuring protein phosphorylation. It uses fluorescence resonance energy transfer.

• Luminex - They use beads sorted by a unique number given to each bead and measured using a fluorescence platform.

• Mass Spectrometry - Used to measure phosphorylation. It is an analytical technique that separates atoms and molecules by their respective masses, and the molecular weight can be obtained using this.

• Flow Cytometry - Used to measure the physical or chemical behavior of cells by suspending the cells into a fluid cytometer.

• Mass Cytometry - It uses mass spectrometry to detect antibodies that are metal conjugated which are bound to the antigens.

• Antibody and Protein Arrays - Antibodies are collected and fixed on a surface, and the interaction between the antibody and the target antigen is detected.

• Phosphoprotein Measurements in Resected Tissues - Immunohistochemistry is used to detect phosphorylation in tissues by using peroxide-conjugated antibodies.

• Transcriptional Profiling - Transcriptional profiling is used to identify stem cells and their progeny. It is also called expression profiling.

Conclusion

Cell signaling is an important property of every living organism. Receptors receive the cell signals, which cause a conformational change resulting in enzymatic activity. Each cell responds to a specific molecule. Cell signals can cause development, immunity, etc. The inability to create proper signals and abnormal responses can cause autoimmune diseases or cancers.