A.
A surge in the cytosolic concentration of free Ca 2+ is triggered by many kinds of cell stimuli, not only those that act through GPCRs. When a sperm fertilizes an egg cell, for example, Ca 2+ channels open, and the resulting rise in cytosolic Ca 2+ triggers the egg to start development; for muscle cells, a signal from a nerve triggers a rise in cytosolic Ca 2+ that initiates muscle contraction; and in many secretory cells, including nerve cells, Ca 2+ triggers secretion. Ca 2+ stimulates all these responses by binding to and influencing the activity of various Ca 2+ -responsive proteins.
B.
The effects of Ca 2+ in the cytosol are largely indirect, in that they are mediated through the interaction of Ca 2+ with various kinds of Ca 2+ -responsive proteins. The most widespread and common of these is calmodulin, which is present in the cytosol of all eukaryotic cells that have been examined, including those of plants, fungi, and protozoa. When Ca 2+ binds to calmodulin, the protein undergoes a conformational change that enables it to interact with a wide range of target proteins in the cell, altering their activities.
C.
One particularly important class of targets for calmodulin is the Ca 2+ /calmodulin-dependent protein kinases (CaM-kinases). When these kinases are activated by binding to calmodulin complexed with Ca 2+ , they influence other processes in the cell by phosphorylating selected proteins.
D.
In the mammalian brain, for example, a neuron-specific CaM-kinase is abundant at synapses, where it is thought to play an important part in some forms of learning and memory. This CaM-kinase is activated by the pulses of Ca 2+ signals that occur during neural activity, and mutant mice that lack the kinase show a marked inability to remember where things are.