| First Author | Wang P | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 12 | Pages | 2627-2641 |
| PubMed ID | 28636948 | Mgi Jnum | J:256248 |
| Mgi Id | MGI:6103390 | Doi | 10.1016/j.celrep.2017.05.088 |
| Citation | Wang P, et al. (2017) PTENalpha Modulates CaMKII Signaling and Controls Contextual Fear Memory and Spatial Learning. Cell Rep 19(12):2627-2641 |
| abstractText | PTEN (phosphatase and tensin homology deleted on chromosome 10) has multiple functions, and recent studies have shown that the PTEN family has isoforms. The roles of these PTEN family members in biologic activities warrant specific evaluation. Here, we show that PTENalpha maintains CaMKII in a state that is competent to induce long-term potentiation (LTP) with resultant regulation of contextual fear memory and spatial learning. PTENalpha binds to CaMKII with its distinctive N terminus and resets CaMKII to an activatable state by dephosphorylating it at sites T305/306. Loss of PTENalpha impedes the interaction of CaMKII and NR2B, leading to defects in hippocampal LTP, fear-conditioned memory, and spatial learning. Restoration of PTENalpha in the hippocampus of PTENalpha-deficient mice rescues learning deficits through regulation of CaMKII. CaMKII mutations in dementia patients inhibit CaMKII activity and result in disruption of PTENalpha-CaMKII-NR2B signaling. We propose that CaMKII is a target of PTENalpha phosphatase and that PTENalpha is an essential element in the molecular regulation of neural activity. |
