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Cited by 36Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersRNA Research and Splicing

NESH Regulates Dendritic Spine Morphology and Synapse Formation

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Bae, Jeomil, Sung, Bong Hwan, Cho, In Ha, Kim, Seon-Myung, Song, Woo Keun·2012·PLoS ONE
DOI 10.1371/journal.pone.0034677PMC PMC3317636
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Abstract

BACKGROUND: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines. CONCLUSIONS/SIGNIFICANCE: NESH is a novel F-actin binding protein that likely plays important roles in the regulation of dendritic spine morphogenesis and synapse formation.

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  • ABI3 is mainly expressed in microglia, but its expression in neurons and interaction with filamentous actin in dendritic spines were observed in primary neuronal cell culture.

    “Although ABI3 is mainly expressed in microglia, its expression in neurons and interaction with filamentous actin (F-actin) in dendritic spines were observed in primary neuronal cell culture (44, 63).”

    From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [63]

    The Results section (Figure 1 and ‘Expression profile of NESH in brain’) shows ABI3/NESH in primary cultured hippocampal neurons and reports its co-localization with F-actin in dendritic spines. The paper also reports F-actin binding, but it does not establish that ABI3 is mainly expressed in microglia; its expression comparison is among brain regions, not cell types. (LLM, conf=0.88)

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  • Overexpression and down-regulation of Abi3 altered spine morphology and synaptic density.

    “Overexpression and down-regulation of Abi3 altered spine morphology and synaptic density (63).”

    From Deletion of <i>Abi3</i> gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [63]

  • Several other proteins known to signal via actin-regulatory pathways, including VCP/neurofibromin, NESH/Abi-3 and Cofilin, drive similar effects on spine structure when either up- or downregulated.

    “As we observe an increase in immature spines upon CYFIP1 overexpression or haploinsufficiency in vitro, it is interesting to note that several other proteins known to signal via actin-regulatory pathways have been shown to drive similar effects on spine structure when either up- or downregulated, including VCP/neurofibromin, NESH/Abi-3 and Cofilin.47,48,57,64, 65, 66, 67”

    From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [64]

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Authors
Bae, J., Sung, B. H., Cho, I. H., Kim, S.-M., & Song, W. K.
Affiliations
  • Gwangju Institute of Science and Technology (KR)
  • Vanderbilt University Medical Center (US)
  • Emory University (US)
Corresponding author
Song, Woo Keun
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-04-02
Volume
7
Issue
4
Pages
e34677
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0034677
PMC
PMC3317636
OpenAlex
W2021766416
Cited by
36
References
8
Citations by year
2025: 1 · 2024: 4 · 2023: 1 · 2022: 14 · 2021: 5 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 1
FWCI
0.92
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • National Research Foundation of Korea
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
nesh, dendritic spine morphogenesis, synaptogenesis, F-actin binding, mushroom spines, spine density, PSD-95, hippocampus, postsynaptic proteins, actin cytoskeleton
MeSH terms
Animals, Hippocampus, Humans, Microfilament Proteins, Actin Cytoskeleton, Nerve Tissue Proteins, Neurons, Protein Binding, Synapses, Gene Expression, Rats, Sprague-Dawley, RNA Interference, Cell Shape, Dendritic Spines, Rats, Protein Interaction Domains and Motifs, Gene Knockdown Techniques, HEK293 Cells

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