The expression of the PDZ protein MALS-1/Velis is regulated by calcium and calcineurin in cerebellar granule cells

Activity-dependent gene expression is thought to be important in shaping neuronal development and in modifying the protein content of neurons. Ca²⁺ entry into neurons appears to be one of the key effectors of activity-dependent gene expression. Among the possible downstream targets of calcium, the protein phosphatase calcineurin represents a prime candidate. We hereby report that in cultured cerebellar granule cells the activation of the Ca²⁺/calcineurin pathway via either voltage- or ligand-operated Ca²⁺ channels regulates MALS-1 and MALS-2 expression at the transcriptional level. These proteins are integral parts of the post-synaptic density and are also involved in receptor trafficking. MALS regulation is not at the level of mRNA stability and does not require de novo protein synthesis, thereby suggesting a direct pathway. These data suggest that Ca²⁺ entry by means of calcineurin is capable of controlling the structure of the post-synaptic density by controlling the expression of key components at the transcriptional level.