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Article: Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome

TitleIncreased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome
Authors
Issue Date2015
Citation
Cell Reports, 2015, v. 11, n. 5, p. 727-736 How to Cite?
Abstract© 2015 The Authors. The PI3K enhancer PIKE links PI3K catalytic subunitsto group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS). Normalizing elevated PIKE protein levels in FXS mice reversed deficits in molecular and cellular plasticity and improved behavior. Notably, PIKE reduction rescued PI3K-dependent and -independent neuronal defects in FXS. We further show that PI3K signaling is increased in a fly model of FXS and that genetic reduction of the Drosophila ortholog of PIKE, CenG1A rescued excessive PI3K signaling, mushroom body defects, and impaired short-term memory in these flies. Our results demonstrate a crucial role of increased PIKE expression in exaggerated mGlu1/5 signaling causing neuronal defects inFXS.
Persistent Identifierhttp://hdl.handle.net/10722/225069

 

DC FieldValueLanguage
dc.contributor.authorGross, Christina-
dc.contributor.authorChang, Chia Wei-
dc.contributor.authorKelly, Seth M.-
dc.contributor.authorBhattacharya, Aditi-
dc.contributor.authorMcBride, Sean M J-
dc.contributor.authorDanielson, Scott W.-
dc.contributor.authorJiang, Michael Q.-
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorYe, Keqiang-
dc.contributor.authorGibson, Jay R.-
dc.contributor.authorKlann, Eric-
dc.contributor.authorJongens, Thomas A.-
dc.contributor.authorMoberg, Kenneth H.-
dc.contributor.authorHuber, Kimberly M.-
dc.contributor.authorBassell, Gary J.-
dc.date.accessioned2016-04-18T11:16:41Z-
dc.date.available2016-04-18T11:16:41Z-
dc.date.issued2015-
dc.identifier.citationCell Reports, 2015, v. 11, n. 5, p. 727-736-
dc.identifier.urihttp://hdl.handle.net/10722/225069-
dc.description.abstract© 2015 The Authors. The PI3K enhancer PIKE links PI3K catalytic subunitsto group 1 metabotropic glutamate receptors (mGlu1/5) and activates PI3K signaling. The roles of PIKE in synaptic plasticity and the etiology of mental disorders are unknown. Here, we show that increased PIKE expression is a key mediator of impaired mGlu1/5-dependent neuronal plasticity in mouse and fly models of the inherited intellectual disability fragile X syndrome (FXS). Normalizing elevated PIKE protein levels in FXS mice reversed deficits in molecular and cellular plasticity and improved behavior. Notably, PIKE reduction rescued PI3K-dependent and -independent neuronal defects in FXS. We further show that PI3K signaling is increased in a fly model of FXS and that genetic reduction of the Drosophila ortholog of PIKE, CenG1A rescued excessive PI3K signaling, mushroom body defects, and impaired short-term memory in these flies. Our results demonstrate a crucial role of increased PIKE expression in exaggerated mGlu1/5 signaling causing neuronal defects inFXS.-
dc.languageeng-
dc.relation.ispartofCell Reports-
dc.titleIncreased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.celrep.2015.03.060-
dc.identifier.scopuseid_2-s2.0-84933670490-
dc.identifier.volume11-
dc.identifier.issue5-
dc.identifier.spage727-
dc.identifier.epage736-
dc.identifier.eissn2211-1247-

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