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| Content Provider | Springer Nature Link |
|---|---|
| Author | Cho, In Ha Lee, Min Jung Kim, Dae Hwan Kim, Bora Bae, Jeomil Choi, Kyu Yeong Kim, Seon Myung Huh, Yun Hyun Lee, Kun Ho Kim, Chong Hyun Song, Woo Keun |
| Copyright Year | 2013 |
| Abstract | Actin plays a fundamental role in the regulation of spine morphology (both shrinkage and enlargement) upon synaptic activation. In particular, actin depolymerization is crucial for the spine shrinkage in NMDAR-mediated synaptic depression. Here, we define the role of SPIN90 phosphorylation/dephosphorylation in regulating actin depolymerization via modulation of cofilin activity. When neurons were treated with NMDA, SPIN90 was dephosphorylated by STEP61 (striatal-enriched protein tyrosine phosphatase) and translocated from the spines to the dendritic shafts. In addition, phosphorylated SPIN90 bound cofilin and then inhibited cofilin activity, suggesting that SPIN90 dephosphorylation is a prerequisite step for releasing cofilin so that cofilin can adequately sever actin filaments into monomeric form. We found that SPIN90 YE, a phosphomimetic mutant, remained in the spines after NMDAR activation where it bound cofilin, thereby effectively preventing actin depolymerization. This led to inhibition of the activity-dependent redistribution of cortactin and drebrin A, as well as of the morphological changes in the spines that underlie synaptic plasticity. These findings indicate that NMDA-induced SPIN90 dephosphorylation and translocation initiates cofilin-mediated actin dynamics and spine shrinkage within dendritic spines, thereby modulating synaptic activity. |
| Starting Page | 4369 |
| Ending Page | 4383 |
| Page Count | 15 |
| File Format | |
| ISSN | 1420682X |
| Journal | Cellular and Molecular Life Sciences |
| Volume Number | 70 |
| Issue Number | 22 |
| e-ISSN | 14209071 |
| Language | English |
| Publisher | Springer Basel |
| Publisher Date | 2013-06-14 |
| Publisher Place | Basel |
| Access Restriction | Subscribed |
| Subject Keyword | Dendritic spines Long-term depression Spine shrinkage Actin depolymerization Cell Biology Biomedicine general Life Sciences Biochemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Molecular Medicine Pharmacology Cellular and Molecular Neuroscience |
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