Determination of dendritic spine morphology by the striatin scaffold protein STRN4 through interaction with the phosphatase PP2A

Liu, Lin; Lo, Louisa Hoi-Ying; Lyu, Q; Lai, Kwok-On

doi:10.1074/jbc.m116.772442

Cited by 30 publications

(32 citation statements)

References 66 publications

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“…In addition, CTTNBP2 is also found to regulate the synaptic distribution of striatin 4 (STRN4) and zinedin, which are the regulatory B subunits of protein phosphatase 2A (PP2A), suggesting that CTTNBP2 targets the PP2A complex to dendritic spines, and together with cortactin regulate spine morphogenesis and synaptic signaling 36,44 . The involvement of these proteins in autism has been speculated 45 , and in support of this, the human STRN4 gene is located in chromosome 19q13.32, which is the locus for a reported deletion in ASD 46 .…”

Section: Accepted Manuscriptmentioning

confidence: 82%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Section: Accepted Manuscriptmentioning

confidence: 82%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Only a few other research groups have addressed the role of PP2A in DS formation. Li et al [51] recently indicated that PP2A is necessary for DS formation in striatal neurons [52]. Liu et al [53] determined that PP2A interacts with the protein PRG-1 at the postsynaptic density not only to modulate synaptic plasticity but also to produce the recruitment of focal adhesion proteins such as Src and paxillin.…”

Section: Discussionmentioning

confidence: 99%

Rapid Estrogen and Progesterone Signaling to Dendritic Spine Formation via Cortactin/Wave1-Arp2/3 Complex

Uzair

Flamini

Sanchez³

2019

Neuroendocrinology

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Background: Synaptic plasticity is the neuronal capacity to modify the function and structure of dendritic spines (DS) in response to neuromodulators. Sex steroids, particularly 17β-estradiol (E2) and progesterone (P4), are key regulators in the control of DS formation through multiprotein complexes including WAVE1 protein, and are thus fundamental for the development of learning and memory. Objectives: The aim of this work was to evaluate the molecular switch Cdk5 kinase/protein phosphatase 2A (PP2A) in the control of WAVE1 protein (phosphorylation/dephosphorylation) and the regulation of WAVE1 and cortactin to the Arp2/3 complex, in response to rapid treatments with E2 and P4 in cortical neuronal cells. Results: Rapid treatment with E2 and P4 modified neuronal morphology and significantly increased the number of DS. This effect was reduced by the use of a Cdk5 inhibitor (Roscovitine). In contrast, inhibition of PP2A with PP2A dominant negative construct significantly increased DS formation, evidencing the participation of kinase/phosphatase in the regulation of WAVE1 in DS formation induced by E2 and P4. Cortactin regulates DS formation via Src and PAK1 kinase induced by E2 and P4. Both cortactin and WAVE1 signal to Arp2/3 complex to synergistically promote actin nucleation. Conclusion: These results suggest that E2 and P4 dynamically regulate neuron morphology through nongenomic signaling via cortactin/WAVE1-Arp2/3 complex. The control of these proteins is tightly orchestrated by phosphorylation, where kinases and phosphatases are essential for actin nucleation and, finally, DS formation. This work provides a deeper understanding of the biological actions of sex steroids in the regulation of DS turnover and neuronal plasticity processes.

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“…The rs10409124 is located on the 13th exon of STRN4, resulting in a substitution of valine by isoleucine at site 568. STRN4 maps at 19q13.2 and is involved in protein domain-specific binding and calmodulin binding (Lin et al, 2017). STRN4 belongs to the striatin family of scaffold proteins that are highly expressed in the nervous system and are also known to form complexes with protein phosphatases and protein kinases (Wong et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

et al. 2020

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Genome-wide association studies have identified more than 150 susceptibility loci for coronary artery disease (CAD); however, there is still a large proportion of missing heritability remaining to be investigated. This study sought to identify population-based genetic variation associated with acute coronary syndromes (ACS) in individuals of Chinese Han descent. We proposed a novel strategy integrating a well-developed risk prediction model into control selection in order to lower the potential misclassification bias and increase the statistical power. An exome-wide association analysis was performed for 1,669 ACS patients and 1,935 healthy controls. Promising variants were further replicated using the existing in silico dataset. Additionally, we performed gene-and pathway-based analyses to investigate the aggregate effect of multiple variants within the same genes or pathways. Although none of the association signals were consistent across studies after Bonferroni correction, one promising variant, rs10409124 at STRN4, showed potential impact on ACS in both European and East Asian populations. Gene-based analysis explored four genes (ANXA7, ZNF655, ZNF347, and ZNF750) that showed evidence for association with ACS after multiple test correction, and identification of ZNF655 was successfully replicated by another dataset. Pathway-based analysis revealed that 32 potential pathways might be involved in the pathogenesis of ACS. Our study identified several candidate genes and pathways associated with ACS. Future studies are needed to further validate these findings and explore these genes and pathways as potential therapeutic targets in ACS.

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Determination of dendritic spine morphology by the striatin scaffold protein STRN4 through interaction with the phosphatase PP2A

Cited by 30 publications

References 66 publications

Dendritic spine actin cytoskeleton in autism spectrum disorder

Dendritic spine actin cytoskeleton in autism spectrum disorder

Rapid Estrogen and Progesterone Signaling to Dendritic Spine Formation via Cortactin/Wave1-Arp2/3 Complex

Exome-Wide Association Study Reveals Several Susceptibility Genes and Pathways Associated With Acute Coronary Syndromes in Han Chinese

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