SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neuronsReportar como inadecuado

SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neurons - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cellular and Molecular Life Sciences

, Volume 70, Issue 22, pp 4369–4383

First Online: 14 June 2013Received: 31 January 2013Revised: 11 May 2013Accepted: 29 May 2013DOI: 10.1007-s00018-013-1391-4

Cite this article as: Cho, I.H., Lee, M.J., Kim, D.H. et al. Cell. Mol. Life Sci. 2013 70: 4369. doi:10.1007-s00018-013-1391-4


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.

KeywordsDendritic spines Long-term depression Spine shrinkage Actin depolymerization Electronic supplementary materialThe online version of this article doi:10.1007-s00018-013-1391-4 contains supplementary material, which is available to authorized users.

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Autor: In Ha Cho - Min Jung Lee - Dae Hwan Kim - Bora Kim - Jeomil Bae - Kyu Yeong Choi - Seon-Myung Kim - Yun Hyun Huh - Ku

Fuente: https://link.springer.com/

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