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Cited by 84Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersProtein Kinase Regulation and GTPase Signaling

Homer is concentrated at the postsynaptic density and does not redistribute after acute synaptic stimulation

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Tao-Cheng, J.-H., Thein, S., Yang, Y., Reese, T.S., Gallant, P.E.·2014·Neuroscience
DOI 10.1016/j.neuroscience.2014.01.066PMC PMC3998121
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Abstract

Homer is a postsynaptic density (PSD) scaffold protein that is involved in synaptic plasticity, calcium signaling and neurological disorders. Here, we use pre-embedding immunogold electron microscopy to illustrate the differential localization of three Homer gene products (Homer 1, 2, and 3) in different regions of the mouse brain. In cross-sectioned PSDs, Homer occupies a layer ∼30-100nm from the postsynaptic membrane lying just beyond the dense material that defines the PSD core (∼30-nm-thick). Homer is evenly distributed within the PSD area along the lateral axis, but not at the peri-PSD locations within 60nm from the edge of the PSD, where type I-metabotropic glutamate receptors (mGluR1 and 5) are concentrated. This distribution of Homer matches that of Shank, another major PSD scaffold protein, but differs from those of other two major binding partners of Homer, type I mGluR and IP3 receptors. Many PSD proteins rapidly redistribute upon acute (2min) stimulation. To determine whether Homer distribution is affected by acute stimulation, we examined its distribution in dissociated hippocampal cultures under different conditions. Both the pattern and density of label for Homer 1, the isoform that is ubiquitous in hippocampus, remained unchanged under high K(+) depolarization (90mM for 2-5min), N-methyl-d-asparic acid (NMDA) treatment (50μM for 2min), and calcium-free conditions (EGTA at 1mM for 2min). In contrast, Shank and calcium/calmodulin-dependent kinase II (CaMKII) accumulate at the PSD upon NMDA treatment, and CaMKII is excluded from the PSD complex under low calcium conditions.

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  • Deeper within the PSD, Shank and Homer proteins self-assemble into a mesh-like matrix characterized by tetrameric coiled-coils, with Homer located 30-100 nm from the postsynaptic membrane and mGluRs concentrated at peri-PSD locations within 60 nm of the edge.

    “Deeper within the PSD, in a region often referred to as the “pallium,” Shank and Homer proteins self-assemble into a mesh-like matrix characterized by tetrameric coiled-coils [42]. Immunogold electron microscopy places Homer in a layer 30–100 nm from the postsynaptic membrane, whereas mGluRs are concentrated at peri-PSD locations within 60 nm of the edge [43].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [43]

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Research works printed but not linked: 39

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Authors
Tao-Cheng, J.-H., Thein, S., Yang, Y., Reese, T. S., & Gallant, P. E.
Affiliations
National Institutes of Health (US)
Corresponding author
Tao-Cheng, J.-H.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2014-04
Volume
266
Pages
80-90
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2014.01.066
PMC
PMC3998121
OpenAlex
W1978364312
Cited by
84
References
42
Citations by year
2026: 7 · 2025: 4 · 2024: 7 · 2023: 9 · 2021: 18 · 2020: 15 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 1
FWCI
2.13
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (Z99 NS999999)
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 › Protein Kinase Regulation and GTPase Signaling
Keywords
Homer, postsynaptic density, synaptic scaffold proteins, shank, metabotropic glutamate receptors, IP3 receptor, CaMKII, synaptic plasticity, NMDA, calcium signaling, hippocampus, protein localization
MeSH terms
Homer Scaffolding Proteins, Animals, Carrier Proteins, Immunohistochemistry, Nerve Tissue Proteins, Immunoblotting, Rats, Sprague-Dawley, Protein Transport, Mice, Rats, Post-Synaptic Density

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