In a multicellular organism, virtually all aspects of cell behavior—metabolism, movement, proliferation, differentiation—are regulated by cell signaling. Transmitting cells produce signaling molecules that are recognized by responding cells, causing them to change their behavior. Intercellular signaling can take place over long distances where the transmitting cell and responding cell are far removed from each other, as when the signaling molecule is a hormone that is secreted and then must travel some distance to be received by responding cells.
Classes of cell signaling
In most cases, the transmitting and responding cells are in close proximity, and here three types of signaling mechanism can be distinguished, as listed below. In the first two cases, the signaling produces a change in gene expression in the responding cell, but in synaptic signaling the result is a change in electric potential of the cell membrane.
• Paracrine signaling. A cell sends a secreted signaling molecule that diffuses over a short distance to bind to receptors on responding cells in the local neighborhood.
• Juxtacrine signaling. The transmitting cell is in direct contact with the responding cell; the signaling molecule is tethered to the surface of the transmitting cell, and is bound by a receptor on the surface of the responding cell.
• Synaptic signaling. This specialized form of signaling occurs between adjacent neurons or between adjacent neuron and muscle cells, and produces changes in membrane potential, notably depolarization.
In paracrine and juxtacrine cell signaling, the transmitting cells and the responding cells are usually different cell types. However, an alternative is for the signaling molecule to bind to a receptor on the surface of the transmitting cell or identical neighbor cells. This type of autocrine signaling can be used to reinforce a signaling decision, or to coordinate decisions by groups of the same kind of cell.
Different types of action by signaling molecules and receptors
Some small, hydrophobic signaling molecules can pass directly through the plasma membrane of the responding cell and bind to intracellular receptors (Figure 1B). In many examples of cell signaling, however, the signaling molecule cannot cross the cell membrane and works by binding to a receptor on the surface of the responding cell. In those cases, the signal is often a soluble molecule that diffuses a short distance before binding to its receptor (Figure 1A). In juxtacrine signaling, however, the signal molecule is anchored in the plasma membrane of the transmitting cell (Figure 1C). Table 1 provides some examples of different cell signaling systems in vertebrates; we will consider details of some mechanisms in the sections below.
Fig1. Three types of relationship between ligand and receptor in cell signaling. (A) Soluble ligand and cell surface receptor. In this type of paracrine signaling, the ligand is often a protein that binds to a transmembrane protein receptor, activating its cytoplasmic tail. (B) Small, soluble ligand and intracellular receptor. In this type of paracrine signaling, the ligand may be a gas (such as nitric oxide) or a protein or steroid that is so small that it can freely pass through membranes. (C) Membrane-bound ligand and cell surface receptor on adjacent cells (juxtacrine signaling). See Table 1 for examples.
Table1. IMPORTANT CLASSES OF VERTEBRATE CELL SIGNALING MOLECULES AND THEIR RECEPTORS
How gene expression is altered
The endpoint of most cell signaling is altered gene expression producing behavioral changes in the responding cells. The usual key to this change, the final step in signal transduction, is activation of a specific transcription factor so that it selectively binds to the DNA of certain target genes to modulate gene expression. One part of a transcription factor protein is used to recognize and bind the target DNA sequence; another part is used to activate gene expression (Box 1).
Box1. TRANSCRIPTION FACTOR STRUCTURE
Activation of the transcription factor that causes the change in gene expression is indirect in the case of signaling pathways that use a cell surface receptor. Binding of a signaling molecule to the receptor induces a change in the receptor’s cytoplasmic domain. The alteration in the receptor activates a signal-transduction pathway that typically culminates in activation (or sometimes inhibition) of a transcription factor. However, as described in the next section, a signaling molecule that passes through the cell membrane and binds directly to an intracellular receptor causes a conformational change in the receptor that directly induces it to become an active transcription factor.
