Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca(2+) signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca(2+), neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca(2+)-ATPase (PMCA), sarco/endoplasmic Ca(2+)-ATPase (SERCA) and secretory pathway Ca(2+)-ATPase (SPCA) are considered efficient line of defense against abnormal Ca(2+) rises. However, their role is not limited only to Ca(2+) transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca(2+)-ATPases to neuropathology, with a special emphasis on mental diseases.