第9章細胞間の情報伝達

When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell. There are many internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis. However, in some cases, such as a viral infection or uncontrolled cell division due to cancer, the cell’s normal checks and balances fail. External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis. This system keeps cells from traveling through the body and proliferating out of control, as happens with tumor cells that metastasize.

Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are immune cells that bind to foreign macromolecules and particles, and target them for destruction by the immune system. Normally, T-cells do not target “self” proteins (those of their own organism), a process that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins. If the receptor of the immature T-cell binds to self proteins, the T-cell undergoes apoptosis and removes the potentially dangerous cell.

Apoptosis is also essential for normal embryological development. In vertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes (Figure 9.15). During the course of normal development, these unneeded cells must be eliminated, enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.

The aberrant signaling often seen in tumor cells is proof that the termination of a signal at the appropriate time can be just as important as the initiation of a signal. One method of stopping a specific signal is to degrade the ligand or remove it so that it can no longer access its receptor. One reason that hydrophobic hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins. These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones from degradation by circulating enzymes.

Inside the cell, many different enzymes reverse the cellular modifications that result from signaling cascades. For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation. Cyclic AMP (cAMP) is degraded into AMP by phosphodiesterase, and the release of calcium stores is reversed by the Ca²⁺ pumps that are located in the external and internal membranes of the cell.

The initiation of a signaling pathway is a response to external stimuli. This response can take many different forms, including protein synthesis, a change in the cell’s metabolism, cell growth, or even cell death. Many pathways influence the cell by initiating gene expression, and the methods utilized are quite numerous. Some pathways activate enzymes that interact with DNA transcription factors. Others modify proteins and induce them to change their location in the cell. Depending on the status of the organism, cells can respond by storing energy as glycogen or fat, or making it available in the form of glucose. A signal transduction pathway allows muscle cells to respond to immediate requirements for energy in the form of glucose. Cell growth is almost always stimulated by external signals called growth factors. Uncontrolled cell growth leads to cancer, and mutations in the genes encoding protein components of signaling pathways are often found in tumor cells. Programmed cell death, or apoptosis, is important for removing damaged or unnecessary cells. The use of cellular signaling to organize the dismantling of a cell ensures that harmful molecules from the cytoplasm are not released into the spaces between cells, as they are in uncontrolled death, necrosis. Apoptosis also ensures the efficient recycling of the components of the dead cell. Termination of the cellular signaling cascade is very important so that the response to a signal is appropriate in both timing and intensity. Degradation of signaling molecules and dephosphorylation of phosphorylated intermediates of the pathway by phosphatases are two ways to terminate signals within the cell.