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- Publisher Website: 10.1016/j.celrep.2015.03.060
- Scopus: eid_2-s2.0-84933670490
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Article: Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome
Title | Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome |
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Authors | |
Issue Date | 2015 |
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 Identifier | http://hdl.handle.net/10722/225069 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Gross, Christina | - |
dc.contributor.author | Chang, Chia Wei | - |
dc.contributor.author | Kelly, Seth M. | - |
dc.contributor.author | Bhattacharya, Aditi | - |
dc.contributor.author | McBride, Sean M J | - |
dc.contributor.author | Danielson, Scott W. | - |
dc.contributor.author | Jiang, Michael Q. | - |
dc.contributor.author | Chan, Chi Bun | - |
dc.contributor.author | Ye, Keqiang | - |
dc.contributor.author | Gibson, Jay R. | - |
dc.contributor.author | Klann, Eric | - |
dc.contributor.author | Jongens, Thomas A. | - |
dc.contributor.author | Moberg, Kenneth H. | - |
dc.contributor.author | Huber, Kimberly M. | - |
dc.contributor.author | Bassell, Gary J. | - |
dc.date.accessioned | 2016-04-18T11:16:41Z | - |
dc.date.available | 2016-04-18T11:16:41Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Cell Reports, 2015, v. 11, n. 5, p. 727-736 | - |
dc.identifier.uri | http://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.language | eng | - |
dc.relation.ispartof | Cell Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Increased Expression of the PI3K Enhancer PIKE Mediates Deficits in Synaptic Plasticity and Behavior in Fragile X Syndrome | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.celrep.2015.03.060 | - |
dc.identifier.scopus | eid_2-s2.0-84933670490 | - |
dc.identifier.volume | 11 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 727 | - |
dc.identifier.epage | 736 | - |
dc.identifier.eissn | 2211-1247 | - |
dc.identifier.isi | WOS:000353902900007 | - |
dc.identifier.issnl | 2211-1247 | - |