Figure 15–5 Various responses induced by the neurotransmitter acetylcholine. (A) The chemical structure of acetylcholine. (B–D) Different cell types are specialized to respond to acetylcholine in different ways. In some cases (B and C), acetylcholine binds to similar receptor proteins (G-protein-coupled receptors; see Figure 15–6), but the intracellular signals produced are interpreted differently in cells specialized for different functions. In other cases (D), the receptor protein is also different (here, an ion-channel-coupled receptor; see Figure 15–6).
There Are Three Major Classes of Cell-Surface Receptor Proteins
Most extracellular signal molecules bind to specific receptor proteins on the surface of the target cells they influence and do not enter the cytosol or nucleus. These cell-surface receptors act as signal transducers by converting an extracellular ligand-binding event into intracellular signals that alter the behavior of the target cell.
Most cell-surface receptor proteins belong to one of three classes, defined by their transduction mechanism. Ion-channel-coupled receptors, also known as transmitter-gated ion channels or ionotropic receptors, are involved in rapid synaptic signaling between nerve cells and other electrically excitable target cells such as nerve and muscle cells (Figure 15–6A). This type of signaling is mediated by a small number of neurotransmitters that transiently open or close an ion channel formed by the protein to which they bind, briefly changing the ion permeability of the plasma membrane and thereby changing the excitability of the postsynaptic target cell. Most ion-channel-coupled receptors belong to a large family of homologous, multipass transmembrane proteins. Because they are discussed in detail in Chapter 11, we will not consider them further here.
G-protein-coupled receptors act by indirectly regulating the activity of a separate plasma-membrane-bound target protein, which is generally either an enzyme or an ion channel. A trimeric GTP-binding protein (G protein) mediates the interaction between the activated receptor and this target protein (Figure 15–6B). The activation of the target protein can change the concentration of one or more small intracellular signaling molecules (if the target protein is an enzyme), or it can change the ion permeability of the plasma membrane (if the target protein is an ion channel). The small intracellular signaling molecules act in turn to alter the behavior of yet other signaling proteins in the cell.
Enzyme-coupled receptors either function as enzymes or associate directly with enzymes that they activate (Figure 15–6C). They are usually single-pass transmembrane proteins that have their ligand-binding site outside the cell and their catalytic or enzyme-binding site inside. Enzyme-coupled receptors are heterogeneous in structure compared with the other two classes; the great majority, however, are either protein kinases or associate with protein kinases, which phosphorylate specific sets of proteins in the target cell when activated.
There are also some types of cell-surface receptors that do not fit easily into any of these classes but have important functions in controlling the specialization of different cell types during development and in tissue renewal and repair in adults. We discuss these in a later section, after we explain how G-protein-coupled receptors and enzyme-coupled receptors operate. First, we continue our general discussion of the principles of signaling via cell-surface receptors.
Numerous intracellular signaling molecules relay signals received by cell-surface receptors into the cell interior. The resulting chain of intracellular signaling events ultimately alters effector proteins that are responsible for modifying the behavior of the cell (see Figure 15–1).