title: Nuclear calcium signaling induces expression of the synaptic organizers Lrrtm1 and Lrrtm2.
abstract: Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a 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 neurons within 2-4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca(2+)/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein 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.
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Hayer
authors.affiliation: From the Department of Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany Hilmar.Bading@uni-hd.de.
authors.forename: Hilmar
authors.initials: H
authors.lastname: Bading
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D015151:Immunoblotting; D008565:Membrane Proteins; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics* / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C561490:LRRTM1 protein, mouse; C561491:LRRTM2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate; D050882:CREB-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D002118:Calcium
keywords: CBP; Ca2+/Calmodulin-dependent Protein Kinase (CaMK); Calcium Signaling; Gene Regulation; Ionotropic Glutamate Receptor; cAMP Response Element-binding Protein (CREB)