Regulation of cpg15 by signaling pathways that mediate synaptic plasticity.
Transcriptional activation is a key link between neuronal activity and long-term synaptic plasticity. Little is known about genes responding to this activation whose products directly effect functional and structural changes at the synapse. cpg15 is an activity-regulated gene encoding a membrane-bound ligand that regulates dendritic and axonal arbor growth and synaptic maturation. We report that cpg15 is an immediate-early gene induced by Ca(2+) influx through NMDA receptors and L-type voltage-sensitive calcium channels. Activity-dependent cpg15 expression requires convergent activation of the CaM kinase and MAP kinase pathways. Although activation of PKA is not required for activity-dependent expression, cpg15 is induced by cAMP in active neurons. CREB binds the cpg15 promoter in vivo and partially regulates its activity-dependent expression. cpg15 is an effector gene that is a target for signal transduction pathways that mediate synaptic plasticity and thus may take part in an activity-regulated transcriptional program that directs long-term changes in synaptic connections.
Fujino
Tadahiro
T
The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Lee
Wei-Chung Allen
WC
Nedivi
Elly
E
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000235:genetics*; D017781:Genes, Immediate-Early / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
D020746:Calcium Channels, L-Type; D017362:Cyclic AMP Response Element-Binding Protein; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C484377:Nrn1 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517598:Camk1 protein, mouse; C517681:Pnck protein, mouse