The Role of Calpains in Regulating Synaptic Transmission

Abstract

Calpains are Ca2+-dependent neutral cysteine proteases involved in the regulation of most physiological functions. Calpain substrates include receptors, kinases, phosphatases, cytoskeletal proteins, and synaptosomal proteins. Some of these undergo complete degradation by calpains, while most undergo limited proteolysis to form stable protein fragments, which lose the properties of the whole molecule and acquire new and sometimes opposite functions. This review shows that because of their ability to perform limited hydrolysis, calpains are involved in neurotransmitter synthesis processes, the packaging of neurotransmitters into synaptic vesicles, regulation of vesicular transport, modulation of neurotransmitter receptors, and neurotransmitter reuptake, as well as in the processes stabilizing and destabilizing the neuron cytoskeleton. Uncontrollable activation of calpains, which occurs in a number of pathologies, can lead to derangement of the regulation of these processes and can even induce nerve cell death.