In this lesson, we'll be learning about the definition of a ligand in cell biology. We'll look at the two types of ligands, intracellular and extracellular, and one example of each.
What Is a Ligand?
Imagine attending a relay race. A woman sprints out of her starting blocks with the baton in hand. She pulls ahead and hands the baton to her teammate. This continues for all four runners during the race. In this scenario, the baton is the signal that the next teammate can start running. It causes a change in the course of action during the race.
Although cells don't run races or use batons, they do have signals that cause different processes to start or stop. These signals are called ligands. Ligands are small molecules that transmit signals in between or within cells. Ligands exert their effects by binding to cellular proteins called receptors. The ligand is like the baton, and the receptor is like the next runner in line. After binding to the ligand, the receptor can then send additional signals to other parts of the cell.
There are two main types of ligands: ligands that bind to receptors inside the cell, called intracellular ligands, and ligands that bind to receptors outside the cell, called extracellular ligands.
The prefix ''intra'' means inside, so intracellular ligands are signaling molecules that bind to receptors inside the cell. Although this might seem obvious that cell signaling takes place inside the cell, most ligands aren't actually able to enter the cell from the outside.
The outer barrier of the cell is called the cell membrane, and it's very good at keeping the cell separate from the environment. The cell membrane is made of tightly packed lipids and prevents large things from entering the cell. The interior of the cell membrane is hydrophobic, meaning it doesn't mix with water. Hydrophobic things only will tolerate contact with other hydrophobic things. So, any signaling molecule that acts intracellularly must be particularly small and mostly hydrophobic to cross the cell membrane. There are a few molecules like this that play an important role in our biology.
Nitric Oxide & Estrogen
Nitric oxide is an important ligand that helps control our blood pressure. Our blood vessels are lined with tiny cells called endothelial cells. Outside the endothelial cells are smooth muscle cells. When smooth muscle cells relax, our blood vessels can enlarge, increasing blood flow and decreasing blood pressure. Likewise, when our smooth muscle cells contract, blood flow decreases and blood pressure increases.
To regulate the contraction and relaxation of blood vessels, endothelial cells produce nitric oxide. This gas is small and hydrophobic and can easily move in and out of the cells. The nitric oxide diffuses into neighboring smooth muscle cells. There, it activates a molecule called cyclic guanosine monophosphate (cGMP), which changes the activity of other proteins in the cell that cause muscle cells to relax and thus increase blood flow.
This nitric oxide pathway is the pathway modulated by the erectile dysfunction drug Viagra. When nitric oxide is present, cGMP is activated to promote smooth muscle relaxation. However, eventually the body will destroy the activated cGMP, and the process resets. Viagra stops the cGMP from being broken down, allowing the signal to persist for longer periods of time, and thus increase blood flow to the penis, causing a longer erection.
Another example of an intracellular ligand is the sex hormone estrogen. Although estrogen is responsible for the secondary sex characteristics of women, it also plays an important role in the cardiovascular, skeletal, metabolic, and nervous systems. Estrogen travels around the body in the blood and diffuses into cells directly through the cell membrane. Once inside the cell, estrogen binds to its receptor, causing it to move into the nucleus where it can attach to DNA and cause changes in gene expression.
Extracellular ligands bind to their receptors on the surface of the cell and do not pass through the cell membrane. These molecules are usually larger and hydrophilic. They do not mix with the hydrophobic lipids present in the cell membrane.
Insulin & Neurotransmitters
An important example of extracellular signaling is insulin. You may have heard of insulin in respect to diabetes. Insulin is a signaling molecule produced by the pancreas that regulates blood glucose levels, among other processes in the body. When blood glucose levels are too high, such as right after we eat a meal, the pancreas secretes insulin into our blood.
Insulin travels through our blood and binds to insulin receptors on cells, particularly in the muscle and liver, where glucose can be stored. Once insulin activates its receptor, changes occur inside the cell that result in glucose transport proteins being brought to the cell membrane. These proteins are used to bring glucose into the cell.
As glucose enters the body cells, blood glucose levels decrease and the body is returned to a balance, or homeostasis. People with diabetes have problems with their insulin signaling. Either their bodies don't make enough insulin or their insulin receptors no longer recognize insulin, so they cannot regulate their blood sugar.
If you've enjoyed this lesson, you have extracellular ligands to thank. Your brain is made of individual cells called neurons. Neurons communicate with each other by releasing small ligands called neurotransmitters. Neurotransmitters diffuse from one neuron to the next, where they bind to receptors. When activated by their neurotransmitters, the receptors allow different ions, such as sodium or chloride, into the neuron, causing changes in cellular responses of the neuron. Without extracellular ligands like neurotransmitters, our neurons could not communicate, and we would not be able to think, feel or carry out any actions.
Ligands are signaling molecules that cause modulation of processes inside cells by binding to receptors. Intracellular ligands, such as nitric oxide and estrogen, are small and hydrophobic and diffuse directly through the cell membrane to activate proteins. Extracellular ligands, such as insulin and neurotransmitters, are large and hydrophilic and can only bind to receptors on the outside of the cell. The receptors then mediate changes internally.