title: Regulation of ania-6 splice variants by distinct signaling pathways in striatal neurons.
abstract: The striatum is a brain region involved in motor control and in diverse forms of implicit memory. It is also involved in the pathogenesis of many significant human disorders, including drug addiction, that are thought to involve adaptive changes in gene expression. We have previously shown that the cyclin L, ania-6, is expressed as at least two splice forms, which are differentially regulated in striatal neurons by different neurotransmitters. Here, we report that ania-6 transcription is mostly regulated via cAMP response element binding protein (CREB), but that signaling pathways that converge on CREB at the transcriptional level produce different effects on splicing and neuronal gene expression. Glutamate induced a long ania-6 mRNA that encodes a truncated form of the cyclin. This effect depended on the activation of NMDA receptors but was independent of both calcium/calmodulin-dependent protein kinases (CaMK) and extracellular regulated kinase (ERK). Forskolin or brain-derived neurotropic factor (BDNF) induced a short ania-6 mRNA, that encodes the full-length cyclin, and this induction depended on ERK. However, KCl-mediated induction of ania-6 short mRNA, which required activation of L-type calcium channels, was independent of ERK but depended on CaMK. These data suggest that different neuronal signals can differentially regulate splicing and that different intracellular pathways can be recruited to yield a given splice variant.
authors.affiliation: Molecular Plasticity Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA. Veronique.Sgambato@ujf-grenoble.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Sgambato
authors.forename: Raia
authors.initials: R
authors.lastname: Minassian
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Steven E
authors.initials: SE
authors.lastname: Hyman
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000502:physiology; D000077546:Roscovitine; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C499077:Ccnl1 protein, rat; D016213:Cyclins; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D011687:Purines; D018808:Transcription Factor AP-1; D000077546:Roscovitine; D018698:Glutamic Acid; D011189:Potassium Chloride; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium