Nuclear Calcium Signaling Induces Expression of the Synaptic Organizers Lrrtm1 and Lrrtm2 [Gene Regulation]

December 19th, 2014 by Hayer, S. N., Bading, H.

Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neuron within 2 to 4 hours after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis, required calcium/calmodulin (CaM) dependent protein kinases and the nuclear calcium signaling target, CREB binding protein (CBP). Analysis of reporter gene constructs revealed a functional CRE in the proximal promoter of Lrrtm2 indicating that, at least Lrrtm2, is regulated by the classical nuclear calcium- CaMKIV-CREB/CBP pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2.