Large multicellular organisms like us need long-range signaling mechanisms to coordinate the behavior of cells in remote parts of the body. Thus, they have evolved cell types specialized for intercellular communication over large distances. The most sophisticated of these are nerve cells, or neurons, which typically extend long, branching processes (axons) that enable them to contact target cells far away, where the processes terminate at the specialized sites of signal transmission known as chemical synapses. When a neuron is activated by stimuli from other nerve cells, it sends electrical impulses (action potentials) rapidly along its axon; when the impulse reaches the synapse at the end of the axon, it triggers secretion of a chemical signal that acts as a neurotransmitter. The tightly organized structure of the synapse ensures that the neurotransmitter is delivered specifically to receptors on the postsynaptic target cell (Figure 15–2C). The details of this synaptic signaling process are discussed in Chapter 11.
A quite different strategy for signaling over long distances makes use of endocrine cells, which secrete their signal molecules, called hormones, into the bloodstream. The blood carries the molecules far and wide, allowing them to act on target cells that may lie anywhere in the body (Figure 15–2D).
Extracellular Signal Molecules Bind to Specific Receptors
Cells in multicellular animals communicate by means of hundreds of kinds of extracellular signal molecules. These include proteins, small peptides, amino acids, nucleotides, steroids, retinoids, fatty acid derivatives, and even dissolved gases such as nitric oxide and carbon monoxide. Most of these signal molecules are released into the extracellular space by exocytosis from the signaling cell, as discussed in Chapter 13. Some, however, are emitted by diffusion through the signaling cell’s plasma membrane, whereas others are displayed on the external surface of the cell and remain attached to it, providing a signal to other cells only when they make contact. Transmembrane signal proteins may operate in this way, or their extracellular domains may be released from the signaling cell’s surface by proteolytic cleavage and then act at a distance.
Regardless of the nature of the signal, the target cell responds by means of a receptor, which binds the signal molecule and then initiates a response in the target cell. The binding site of the receptor has a complex structure that is shaped to recognize the signal molecule with high specificity, helping to ensure that the receptor responds only to the appropriate signal and not to the many other signaling molecules surrounding the cell. Many signal molecules act at very low concentrations (typically ≤ 10–8 M), and their receptors usually bind them with high affinity (dissociation constant Kd ≤ 10–8 M; see Figure 3–44).
In most cases, receptors are transmembrane proteins on the target-cell surface. When these proteins bind an extracellular signal molecule (a ligand), they become activated and generate various intracellular signals that alter the behavior of the cell. In other cases, the receptor proteins are inside the target cell, and the signal molecule has to enter the cell to bind to them: this requires that the signal molecule be sufficiently small and hydrophobic to diffuse across the target cell’s plasma membrane (Figure 15–3). This chapter focuses primarily on signaling through cell-surface receptors, but we will briefly describe signaling through intracellular receptors later in the chapter.
Each Cell Is Programmed to Respond to Specific Combinations of Extracellular Signals
A typical cell in a multicellular organism is exposed to hundreds of different signal molecules in its environment. The molecules can be soluble, bound to the extracellular matrix, or bound to the surface of a neighboring cell; they can be stimulatory or inhibitory; they can act in innumerable different combinations; and they can influence almost any aspect of cell behavior. The cell responds to this blizzard of signals selectively, in large part by expressing only those receptors and intracellular signaling systems that respond to the signals that are required for the regulation of that cell.