《10.1007_s00018-013-1391-4》.pdf

Cell. Mol. Life Sci. (2013) 70:4369–4383 DOI 10.1007/s00018-013-1391-4 Cellular and Molecular Life Sciences RESEARCH ARTICLE SPIN90 dephosphorylation is required for cofilin‑mediated actin depolymerization in NMDA‑stimulated hippocampal neurons In Ha Cho · Min Jung Lee · Dae Hwan Kim · Bora Kim · Jeomil Bae · Kyu Yeong Choi · Seon‑Myung Kim · Yun Hyun Huh · Kun Ho Lee · Chong‑Hyun Kim · Woo Keun Song Received: 31 January 2013 / Revised: 11 May 2013 / Accepted: 29 May 2013 / Published online: 14 June 2013 © Springer Basel 2013 Abstract Actin plays a fundamental role in the regula- adequately sever actin filaments into monomeric form. tion of spine morphology (both shrinkage and enlarge- We found that SPIN90 YE, a phosphomimetic mutant, ment) upon synaptic activation. In particular, actin remained in the spines after NMDAR activation where it depolymerization is crucial for the spine shrinkage in bound cofilin, thereby effectively preventing actin depo- NMDAR-mediated synaptic depression. Here, we define lymerization. This led to inhibition of the activity-depend- the role of SPIN90 phosphorylation/dephosphorylation ent redistribution of cortactin and drebrin A, as well as in regulating actin depolymerization via modulation of of the morphological changes in the spines that underlie cofilin activity. When neurons were treated with NMDA, synaptic plasticity. These findings indicate that NMDA- SPIN90 was dephosphorylated by STEP61 (striatal- induced SPIN90 dephosphorylation and translocation ini- enriched protein tyrosine phosphatase) and translocated tiates cofilin-mediated actin d