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Cited by 2Neuroscience and Neuropharmacology ResearchMicrotubule and mitosis dynamicsNeuroinflammation and Neurodegeneration Mechanisms

Tubulin and GTP Are Crucial Elements for Postsynaptic Density Construction and Aggregation

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Suzuki, Tatsuo, Fujii, Toshihiro, Kametani, Kiyokazu, Li, Weidong, Tabuchi, Katsuhiko·2025·Journal of Neurochemistry
DOI 10.1111/jnc.70085PMC PMC12093452
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Abstract

In our previous experiments on the postsynaptic density lattice (PSDL), which is thought to serve as the backbone structure for the PSD, we suggested that tubulin plays a fundamental role in the PSD structure at excitatory synapses. In this study, we further reveal an unrecognized characteristic of tubulin within the PSD. First, using electron microscopy, we identified an interaction between postsynaptic structures (PSDL and PSD) and polymerizing microtubules, which led to the binding of polymerizing microtubules to PSDL and PSD. In turn, this interaction induced changes in the microtubule morphology. These results support earlier findings suggesting that microtubules transiently intruding into the spine head can associate with PSDs, inducing structural changes in the PSD. Next, we observed that the structural integrity of both PSD and PSDL was compromised upon exposure to GTP and microtubule‐affecting reagents. These findings reinforce the idea that tubulin is a crucial building block of the PSD architecture. Moreover, we found that PSD aggregation was enhanced following interactions with polymerizing tubulin and was disintegrated upon treatment with GTP and microtubule‐affecting reagents. These results indicate that microtubules also play a key role in PSD aggregation in vitro. Collectively, our study highlights the involvement of tubulin in the construction, function (specifically its interaction with polymerizing microtubules), and aggregation of the PSD, which may impact both physiological and pathological conditions. Furthermore, our in vitro findings suggest that GTP can either destroy or induce the enlargement and reorganization of PSD structures, depending on its interaction with growing microtubules. image

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  • These findings support a view of the PSD as an inherently dynamic structure that balances disassembly and reconstruction, with the tubulin-microtubule system and GTP availability acting as modulators of PSD maintenance and reorganization.

    “Together, these findings support a view of the PSD as an inherently dynamic structure that balances disassembly and reconstruction, with the tubulin-microtubule system and GTP availability acting as modulators of PSD maintenance and reorganization [38].”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [38]

  • Recent in vitro work suggests that the PSD may be dynamically maintained by interactions between a tubulin-containing PSD lattice/backbone and polymerizing microtubules.

    “Recent in vitro work suggests that the PSD may be dynamically maintained not only by canonical scaffold assemblies, but also by interactions between a tubulin-containing PSD lattice/backbone and polymerizing microtubules.”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [38]

  • Suzuki et al. reported physical associations between postsynaptic structures and growing microtubules, and found that exposing PSD/PSD-lattice preparations to GTP and microtubule-affecting reagents compromises PSD structural integrity, with GTP driving disassembly in the absence of polymerizing tubulin and enlargement/reorganization when polymerizing microtubules are available.

    “Using electron microscopy, Suzuki et al. reported physical associations between postsynaptic structures and growing microtubules, consistent with a model in which transient microtubule intrusions into spine heads can couple to PSD structural remodeling. Notably, the authors found that exposing PSD/PSD-lattice preparations to GTP and microtubule-affecting reagents compromises PSD structural”

    From Molecular Physiology of the Neuronal Synapse (2026) · cites this paper as [38]

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Cited by

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Authors
Suzuki, T., Fujii, T., Kametani, K., Li, W., & Tabuchi, K.
Affiliations
  • Shinshu University (JP)
  • Rakuno Gakuen University (JP)
  • Shanghai Jiao Tong University (CN)
Corresponding author
Suzuki, Tatsuo
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2025-05
Volume
169
Issue
5
Pages
e70085-e70085
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.70085
PMC
PMC12093452
OpenAlex
W4410547827
Cited by
2
References
49
Citations by year
2026: 1 · 2025: 1
FWCI
0.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neurochemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (JP22K06428)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
postsynaptic density, tubulin, GTP, microtubules, excitatory synapses, dendritic spines, microtubule assembly, synaptic structure
MeSH terms
Animals, Cells, Cultured, Guanosine Triphosphate, Hippocampus, Microtubules, Tubulin, Rats, Post-Synaptic Density

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