CALCINEURIN - CALCIUM-BINDING AND CALMODULIN-BINDING PROTEIN OF THE NERVOUS-SYSTEM

The inhibitory protein that binds calmodulin and thus prevents activation of several Ca2+-dependent enzymes by calmodulin is shown to also bind four Ca2+ per mol of protein with high affinity [K(d)≤ 10-6 M]. On the basis of its Ca2+ -binding properties and its localization to nervous tissue, the inhibitory protein is now called 'calcineurin.' Calcineurin is composed of two subunits: calcineurin A [61,000 M(r)] which interacts with calmodulin in a Ca2+ -dependent fashion, and calcineurin B[15,000 M(r)] which binds Ca2+. The interaction of calcineurin A with calcineurin B is independent of Ca2+ or Mg2+. The dual interaction of calcineurin A with two different Ca2+ -binding components and the high affinity of calcineurin for Ca2+ suggest a possible role for calcineurin in the regulation of free Ca2+ concentrations in the nervous system. Calcineurin may thereby modulate the release and action of neurotransmitters.