Journal
EMBO JOURNAL
Volume 29, Issue 16, Pages 2827-2840Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.160
Keywords
AMPA receptors; hippocampus; LTD; NMDA; receptors; spines
Categories
Funding
- NIH [U24NS050606]
- National Institute of Mental Health [MH070417]
- Spanish Ministry of Science and Innovation [SAF-2008-04616, SAF-2009-05558-E]
- Fondation Bettencourt-Schuller (France)
Ask authors/readers for more resources
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 receptordependent 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. The EMBO Journal (2010) 29, 2827-2840. doi: 10.1038/ emboj. 2010.160; Published online 13 July 2010
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available