EXPRESSION REGULATION OF A NOVEL Ca super(2+) BINDING PROTEIN CALMYRIN 2 (Cib2) INDICATES ITS FUNCTION IN NMDA RECEPTOR MEDIATED Ca super(2+) SIGNALING

Calmyrin 2 (CaMy2, Cib2) represents a novel calmyrin subfamily of Ca super(2+) binding proteins that coordinate Ca super(2+) in the BF-hand motives. CaMy2 mRNA was recently detected in brain, but nothing is known about CaMy2 protein localization and properties in the brain. We have cloned CaMy2 from rat brain, demonstrated CaMy2 Ca super(2+)-sensor properties and determined its neuronal pattern of rat brain expression. CaMy2 protein is expressed mainly in hippocampal neurons and localizes together with Golgi apparatus and dendrite markers. Our studies in primary cultures of hippocampal neurons demonstrate that expression of CaMy2 protein is induced upon neuronal activation with pharmacological agents that stimulate Ca super(2+) influx through such types of Ca super(2+) channels as glutamate excitatory receptors and voltage-operated Ca super(2+) channels. In addition, increase in CaMy2 protein level was induced by soluble amyloid beta and BDNF. However, most prominent increase in CaMy2 protein (7-fold), and mRNA (2-fold) occurs upon stimulation of NMDA receptor (NMDAR). The induction is blocked by translation inhibitors, specific antagonists of NMDAR, the Ca super(2+)-ch-elator BAPTA, and inhibitors of ERK1/2 and PKC, kinases transmitting NMDAR-linked Ca super(2+) signal. Our results show that CaMy2 level is controlled by NMDAR and Ca super(2+) and suggest CaMy2 role in Ca super(2+) signaling underlying NMDAR activation.