Cytosolic Ca2+Buffers Are Inherently Ca2+Signal Modulators

For precisely regulating intracellular Ca 2+ signals in a time- and space-dependent manner, cells make use of various components of the "Ca 2+ signaling toolkit," including Ca 2+ entry and Ca 2+ extrusion systems. A class of cytosolic Ca 2+ -binding proteins termed Ca 2+ buffers serves as modulators of such, mostly short-lived Ca 2+ signals. Prototypical Ca 2+ buffers include parvalbumins (α and β isoforms), calbindin-D9k, calbindin-D28k, and calretinin. Although initially considered to function as pure Ca 2+ buffers, that is, as intracellular Ca 2+ signal modulators controlling the shape (amplitude, decay, spread) of Ca 2+ signals, evidence has accumulated that calbindin-D28k and calretinin have additional Ca 2+ sensor functions. These other functions are brought about by direct interactions with target proteins, thereby modulating their targets' function/activity. Dysregulation of Ca 2+ buffer expression is associated with several neurologic/neurodevelopmental disorders including autism spectrum disorder (ASD) and schizophrenia. In some cases, the presence of these proteins is presumed to confer a neuroprotective effect, as evidenced in animal models of Parkinson's or Alzheimer's disease.