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PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression
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PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression
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PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression
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Journal Article
PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression
2010
Overview
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.
Esteban and coworkers describe a novel role for the lipid phosphatase PTEN in synaptic physiology through regulation of AMPA receptors. Interestingly, this appears to be connected to an NMDAR‐induced, PDZ‐mediated PTEN recruitment to PSD‐95.
Publisher
John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ Animals
/ Disks Large Homolog 4 Protein
/ EMBO20
/ EMBO27
/ Intracellular Signaling Peptides and Proteins - metabolism
/ Long-Term Synaptic Depression
/ LTD
/ Membrane Proteins - metabolism
/ Proteins
/ PTEN Phosphohydrolase - analysis
/ PTEN Phosphohydrolase - metabolism
/ Rats
/ Receptors, AMPA - metabolism
/ Receptors, N-Methyl-D-Aspartate - metabolism
/ Spine
/ spines
