A novel calcineurin splice variant that modifies calcineurin activity

Calcineurin is a Ca(2+)/calmodulin dependent phosphoprotein phosphatase implicated in a wide range of disorders. Here, we report the cloning of a novel calcineurin A alpha splice variant that lacks both the catalytic and calcineurin B binding domains. Biochemical analysis revealed a stimulating effect on calcineurin activity at low calcium concentrations as well as protein-protein interaction with the catalytic calcineurin holoenzyme. By Western blot analysis, expression of similar short splice variants could be seen in the spinal cord of an animal model of familial amyotrophic lateral sclerosis, suggesting a role of these new variants in motor neuron disease.