PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression.
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.
Jurado
Sandra
S
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
Benoist
Marion
M
Lario
Argentina
A
Knafo
Shira
S
Petrok
Cortney N
CN
Esteban
José A
JA
D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D036881:Long-Term Synaptic Depression; D008565:Membrane Proteins / Q000378:metabolism; D054731:PDZ Domains; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013131:Spine / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat