title: mRNA binding protein staufen 1-dependent regulation of pyramidal cell spine morphology via NMDA receptor-mediated synaptic plasticity.
abstract: Staufens (Stau) are RNA-binding proteins involved in mRNA transport, localization, decay and translational control. The Staufen 1 (Stau1) isoform was recently identified as necessary for the protein synthesis-dependent late phase long-term potentiation (late-LTP) and for the maintenance of mature dendritic spines and synaptic activity in hippocampal CA1 pyramidal cells, strongly suggesting a role of mRNA regulation by Stau1 in these processes. However, the causal relationship between these impairments in synaptic function (spine shape and basal synaptic activity) and plasticity (late-LTP) remains unclear. Here, we determine that the effects of Stau1 knockdown on spine shape and size are mimicked by blocking NMDA receptors (or elevating extracellular Mg2+) and that Stau1 knockdown in the presence of NMDA receptor blockade (or high Mg2+) has no further effect on spine shape and size. Moreover, the effect of Stau1 knockdown on late-LTP cannot be explained by these effects, since when tested in normal medium, slice cultures that had been treated with high Mg2+ (to impair NMDA receptor function) in combination with a control siRNA still exhibited late-LTP, while siRNA to Stau1 was still effective in blocking late-LTP. Our results indicate that Stau1 involvement in spine morphogenesis is dependent on ongoing NMDA receptor-mediated plasticity, but its effects on late-LTP are independent of these changes. These findings clarify the role of Stau1-dependent mRNA regulation in physiological and morphological changes underlying long-term synaptic plasticity in pyramidal cells.
authors.affiliation: Department of Physiology, Université de Montréal, Montreal, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lebeau
authors.forename: Luc
authors.initials: L
authors.lastname: DesGroseillers
authors.forename: Wayne
authors.initials: W
authors.lastname: Sossin
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C492186:Stau1 protein, rat; D005576:Colforsin; D008274:Magnesium