Chemotaxis

The human genome encodes about 1,000 different types of GPCRs. In addition to transmitting sense information to the brain, some of the molecules act as "map readers." Different regions of the body are marked by specific molecules. Slight

Humans have more than 40 types of chemokines, small signaling molecules that are used as a guidance system through the body. Chemokines have a typical "Greek key" structure (A), resembling a decorative pattern commonly used in ancient Greece (B).

changes in their intensity can be detected thanks to the signal-amplifying qualities of GPCRs. This influences cell migrations the same way that "sniffing" helps a person move toward the source of a smell. Migrations based on moving toward (or away from) higher concentrations of a molecule are called chemotaxis.

Chemotaxis is used throughout the development of the embryo and in some key body systems over a person's lifetime. One of the most obvious cases is the immune system, in which white blood cells learn to recognize and track down invading viruses and bacteria. Receptors on their surfaces recognize fragments of bacteria or diseased cells that need to be found and digested. Another type of receptor detects chemokines, small molecules secreted by other cells. Chemokine signals may be released at sites of infections, like an alarm that summons police to the location of a crime. They are also secreted by tissues such as lymph nodes, which act as training ground and meeting point for immune system cells. Cells need to enter the nodes but only gain access if they can receive chemotactic signals. The same system helps them find partner cells once they are inside. T and B cells (two types of white blood cells) have to meet up in lymph nodes to activate immune responses, and they are guided there by chemokine receptors.

More than 40 types of chemokines have been discovered in human cells. They usually begin as parts of larger proteins; after being cut out or whittled down, they are secreted from the cell. All of them are small molecules, and all contain a "Greek key" structure named after a decorative pattern used widely in ancient Greece. The structure consists of three beta sheets lined up next to each other and an alpha helix that lies cross-wise over the top. A few examples of chemokines and their functions are listed as follows:

• Monocyte chemoattractant protein-1 tells white blood cells called monocytes to leave the bloodstream and enter surrounding tissue. As this happens, the cells specialize into macrophages: or cells that destroy foreign particles by digesting them.

• Interleukin-8 prompts the migration of another type of blood cell, called a neutrophil, out of the bloodstream.

• C chemokines attract immature forms of T cells to the thymus, where they are trained to recognize the difference between the body's native molecules and foreign ones.

• Fractalkine is secreted by cells in the surface layer (en-dothelium) of the linings of blood and lymph vessels. Unlike other chemokines, it often remains attached to the cell by a long tether-like tail. As well as attracting immune system cells, fractalkine helps attach them to endothelial cells.

Chemotaxis is also known to play a role in cancer. When cancer cells leave a tumor in a process called metastasis, they do not settle just anywhere in the body. Specific types of cancer cells have preferred tissues to which they migrate. Sometimes the reason for their destinations is easy to figure out; cells from colon cancer tumors, for example, pass through the liver. They are too large to leave, so they get stuck and often spawn a new tumor in this organ. In other cases, tissues are invaded because they have chemokines that receptors on the cancer cells recognize. Researchers hope that by identifying the signals and re ceptors, they will learn to disrupt them and block the process of metastasis, which is the most frequent cause of death in many types of cancer.

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