Cytosolic Ca Buffers Are Inherently Ca Signal Modulators.

For precisely regulating intracellular Ca signals in a time- and space-dependent manner, cells make use of various components of the "Ca signaling toolkit," including Ca entry and Ca extrusion systems. A class of cytosolic Ca-binding proteins termed Ca buffers serves as modulators of such, mostly short-lived Ca signals. Prototypical Ca buffers include parvalbumins (α and β isoforms), calbindin-D9k, calbindin-D28k, and calretinin. Although initially considered to function as pure Ca buffers, that is, as intracellular Ca signal modulators controlling the shape (amplitude, decay, spread) of Ca signals, evidence has accumulated that calbindin-D28k and calretinin have additional Ca sensor functions. These other functions are brought about by direct interactions with target proteins, thereby modulating their targets' function/activity. Dysregulation of Ca 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.