2.4 Exocytosis and the secretory pathways
Exocytosis is the process by which molecules are released to the outside of the cell. This includes the release of proteins to the plasma membrane and the release of secreted molecules into the extracellular fluid. All eukaryotic cells need a system to transport molecules to their plasma membrane, and many cells secrete proteins into the extracellular environment. In addition, cells in multicellular organisms communicate with each other via a variety of signalling molecules, which are released in appropriate circumstances. Intercellular signalling is effected by hormones, cytokines and other small signalling molecules that are released from secretory vesicles. Even within the nervous system, which we think of as an electrochemical signalling network, the transmission of a signal from one cell to another occurs by the secretion of neurotransmitters into the synaptic cleft, in response to the arrival of an action potential.
Biologists distinguish two basic types of exocytosis. Constitutive secretion is carried out by all cells and serves to transfer molecules from the Golgi network to the outer surface of the cell. It is the default pathway for most molecules bound for the plasma membrane. Regulated secretion occurs in response to specific conditions, signals or biochemical triggers, and is the process underlying the release of cytokines, hormones, neurotransmitters and other small signalling molecules, such as histamine (Figure 11). (Cytokines are soluble extracellular molecules that act locally on cells, whereas hormones are carried by the bloodstream to distant cells. Although secretion usually implies the release of soluble molecules, these pathways also transfer membrane-associated molecules to the cell surface.) One should note in passing that constitutive secretion is not an unregulated process; it is just that the rate of release of the molecules to the cell surface depends on their rate of production, which is regulated by transcription and translation, i.e. at an earlier stage in the pathway.
Identify the fundamental difference between constitutive and regulated secretion, in terms of their function within an organism and the ways in which this is regulated.
Constitutive secretion is a process concerned with the function of the individual cell, and is therefore primarily regulated by the mechanisms of protein production, which are intrinsic to the cell. Regulated secretion is related to a cell's interactions with other cells and therefore is responsive to external stimuli.
In mammals, the release of insulin by β cells of the pancreatic islets of Langerhans, in response to variations in blood glucose concentration, is a good example of regulated secretion. Insulin is retained in secretory vesicles that are triggered to fuse with the plasma membrane in response to a rise in intracellular Ca+ concentration. Briefly, the series of interactions that links the concentration of blood glucose to the rate of insulin secretion is as follows:
A rise in blood glucose causes the ATP: ADP ratio in the β cell to rise, which closes a K+ channel in the plasma membrane.
The resulting change in the β cell's membrane potential opens a Ca2+ channel, causing a rise in intracellular Ca2+ concentration and the secretion of insulin.
The way in which Ca2+ controls the fusion of vesicles with the plasma membrane is discussed in Section 7.2, in relation to the release of neurotransmitters from synaptic vesicles.