Abstract
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.