PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression

Sandra Jurado, Marion Benoist, Argentina Lario, Shira Knafo, Cortney N. Petrok, José A. Esteban

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is an important regulator of phosphatidylinositol-(3,4,5,)-trisphosphate signalling, which controls cell growth and differentiation. However, PTEN is also highly expressed in the adult brain, in which it can be found in dendritic spines in hippocampus and other brain regions. Here, we have investigated specific functions of PTEN in the regulation of synaptic function in excitatory hippocampal synapses. We found that NMDA receptor activation triggers a PDZ-dependent association between PTEN and the synaptic scaffolding molecule PSD-95. This association is accompanied by PTEN localization at the postsynaptic density and anchoring within the spine. On the other hand, enhancement of PTEN lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses. This activity is specifically required for NMDA receptor-dependent long-term depression (LTD), but not for LTP or metabotropic glutamate receptor-dependent LTD. Therefore, these results reveal PTEN as a regulated signalling molecule at the synapse, which is recruited to the postsynaptic membrane upon NMDA receptor activation, and is required for the modulation of synaptic activity during plasticity.

Original languageEnglish
Pages (from-to)2827-2840
Number of pages14
JournalEMBO Journal
Volume29
Issue number16
DOIs
StatePublished - 18 Aug 2010
Externally publishedYes

Keywords

  • AMPA receptors
  • LTD
  • NMDA receptors
  • hippocampus
  • spines

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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