title: PTEN counteracts PIP3 upregulation in spines during NMDA-receptor-dependent long-term depression.
abstract: Phosphoinositide 3-kinase (PI3K) and PTEN have been shown to participate in synaptic plasticity during long-term potentiation (LTP) and long-term depression (LTD), respectively. Nevertheless, the dynamics of phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) and the regulation of its synthesis and degradation at synaptic compartments is far from clear. Here, we have used fluorescence resonance energy transfer (FRET) imaging to monitor changes in PIP3 levels in dendritic spines from CA1 hippocampal neurons under basal conditions and upon induction of NMDA receptor (NMDAR)-dependent LTD and LTP. We found that PIP3 undergoes constant turnover in dendritic spines. Contrary to expectations, both LTD and LTP induction trigger an increase in PIP3 synthesis, which requires NMDARs and PI3K activity. Using biochemical methods, the upregulation of PIP3 levels during LTP was estimated to be twofold. However, in the case of LTD, PTEN activity counteracts the increase in PIP3 synthesis, resulting in no net change in PIP3 levels. Therefore, both LTP and LTD signaling converge towards PIP3 upregulation, but PTEN acts as an LTD-selective switch that determines the outcome of PIP3 accumulation.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Arendt
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid 28049, Spain.
authors.forename: Marion
authors.initials: M
authors.lastname: Benoist
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid 28049, Spain.
authors.forename: Argentina
authors.initials: A
authors.lastname: Lario
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid 28049, Spain.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Draffin
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid 28049, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autónoma de Madrid (UAM), Madrid 28049, Spain jaesteban@cbm.csic.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Esteban
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D018129:Phosphatidylinositol Phosphates; D016194:Receptors, N-Methyl-D-Aspartate; C060974:phosphatidylinositol 3,4,5-triphosphate; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase
keywords: FRET; Hippocampus; PI3K; PTEN; Synaptic plasticity