SPIN90 Phosphorylation Modulates Spine Structure and Synaptic Function

Cho, In Ha; Kim, Dae Hwan; Lee, Min-Jung; Bae, Jeomil; Lee, Kun Ho; Song, Woo Keun

doi:10.1371/journal.pone.0054276

Cited by 14 publications

(25 citation statements)

References 48 publications

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“…NCKIPSD has been evidenced to be involved in the building and maintenance of dendritic spines and modulation of synaptic activity in neurones (33).…”

Section: Discussionmentioning

confidence: 99%

“…showed evidence as an eQTL for AMT, FAM212A, GPX1, NCKIPSD and RNF123 across multiple brain tissues (Supplementary File 1: Tables S5-7). As an example, NCKIPSD encodes a protein involved in the building and maintenance of dendritic spines and modulates neuronal synaptic activity (33 Figure 3). DCC encodes a receptor involved in guiding neuronal growth and is highly expressed in the brain (34).…”

Section: Figure 2 Forest Plot Showing Gwas Associations Of Rs12658032mentioning

confidence: 99%

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Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Powell

Martin

Thapar

et al. 2020

Preprint

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Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p=5x10 -8 ) SNPs in the meta-analysis that were also strongly associated (p=5x10 -4 ) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were identified that were associated with each disorder separately (p=5x10 -4 ) and in the cross-disorder meta-analysis (p=5x10 -8 ). Nine of these SNPs had not been reported previously in either individual GWAS and can be considered as novel signals. Evidence supported nine of the fourteen SNPs acting as eQTL and two of the SNPs as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel regions of the genome that may be implicated in this overlap.

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“…NCKIPSD has been evidenced to be involved in the building and maintenance of dendritic spines and modulation of synaptic activity in neurones (33).…”

Section: Discussionmentioning

confidence: 99%

Section: Figure 2 Forest Plot Showing Gwas Associations Of Rs12658032mentioning

confidence: 99%

Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Powell

Martin

Thapar

et al. 2020

Preprint

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“…SPIN90/WISH [SH3 protein interacting with Nck, 90 kDa/ Wiskott-Aldrich syndrome protein (WASP) interacting SH3 protein] is another scaffold regulator of actin polymerization in dendritic spines. Overexpression of SPIN90 in cultured neurons increases the number and length of dendritic filopodia/ spines via an N-WASP-independent mechanism, while knockdown of its expression and in knockout mice dendritic spine density and maturation is reduced (81,236,275). SPIN90 binds to PSD-95 and Shank and might work as their downstream effector on spine morphogenesis (81,236,275).…”

Section: A Actin Binding and Cytoskeletal Proteinsmentioning

confidence: 99%

Dendritic Spines: The Locus of Structural and Functional Plasticity

Sala

Segal

2014

Physiological Reviews

404

376

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The introduction of high-resolution time lapse imaging and molecular biological tools has changed dramatically the rate of progress towards the understanding of the complex structure-function relations in synapses of central spiny neurons. Standing issues, including the sequence of molecular and structural processes leading to formation, morphological change, and longevity of dendritic spines, as well as the functions of dendritic spines in neurological/psychiatric diseases are being addressed in a growing number of recent studies. There are still unsettled issues with respect to spine formation and plasticity: Are spines formed first, followed by synapse formation, or are synapses formed first, followed by emergence of a spine? What are the immediate and long-lasting changes in spine properties following exposure to plasticity-producing stimulation? Is spine volume/shape indicative of its function? These and other issues are addressed in this review, which highlights the complexity of molecular pathways involved in regulation of spine structure and function, and which contributes to the understanding of central synaptic interactions in health and disease.

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“…Interestingly, the maintenance of LTD is blocked by inhibiting actin depolymerization, as evidenced by the finding that long-lasting forms of LTD are associated with a decrease in filamentous F-actin content in spines (Star et al, 2002 ). Previous studies using neuron cultures have suggested that SPIN90, an ABP is also involved in LTD (Cho et al, 2013a , b ). In this study, we investigated the role of SPIN90 in synapse and behavior by using Spin90 -KO mice.…”

Section: Discussionmentioning

confidence: 98%

SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus

Kim

Kang

Kim

et al. 2017

Front. Mol. Neurosci.

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The importance of actin-binding proteins (ABPs) in the regulation of synapse morphology and plasticity has been well established. SH3 protein interacting with Nck, 90 kDa (SPIN90), an Nck-interacting protein highly expressed in synapses, is essential for actin remodeling and dendritic spine morphology. Synaptic targeting of SPIN90 to spine heads or dendritic shafts depends on its phosphorylation state, leading to blockage of cofilin-mediated actin depolymerization and spine shrinkage. However, the physiological role of SPIN90 in long-term plasticity, learning and memory are largely unknown. In this study, we demonstrate that Spin90-knockout (KO) mice exhibit substantial deficits in synaptic plasticity and behavioral flexibility. We found that loss of SPIN90 disrupted dendritic spine density in CA1 neurons of the hippocampus and significantly impaired long-term depression (LTD), leaving basal synaptic transmission and long-term potentiation (LTP) intact. These impairments were due in part to deficits in AMPA receptor endocytosis and its pre-requisites, GluA1 dephosphorylation and postsynaptic density (PSD) 95 phosphorylation, but also by an intrinsic activation of Akt-GSK3β signaling as a result of Spin90-KO. In accordance with these defects, mice lacking SPIN90 were found to carry significant deficits in object-recognition and behavioral flexibility, while learning ability was largely unaffected. Collectively, these findings demonstrate a novel modulatory role for SPIN90 in hippocampal LTD and behavioral flexibility.

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SPIN90 Phosphorylation Modulates Spine Structure and Synaptic Function

Cited by 14 publications

References 48 publications

Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: A GWAS meta-analysis

Dendritic Spines: The Locus of Structural and Functional Plasticity

SPIN90 Modulates Long-Term Depression and Behavioral Flexibility in the Hippocampus

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