title: SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neurons.
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.
authors.affiliation: Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-Gu, Gwangju, 500-712, Korea.
authors.forename: In Ha
authors.initials: IH
authors.lastname: Cho
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Jeomil
authors.initials: J
authors.lastname: Bae
authors.forename: Kyu Yeong
authors.initials: KY
authors.lastname: Choi
authors.forename: Seon-Myung
authors.initials: SM
authors.lastname: Kim
authors.forename: Yun Hyun
authors.initials: YH
authors.lastname: Huh
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Chong-Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051338:Cofilin 1 / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D051338:Cofilin 1; D009124:Muscle Proteins; C486062:NCKIPSD protein, human; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; C489930:PTPN5 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor