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J Neurochem. 2018 Feb;144(4):390-407. doi: 10.1111/jnc.14254. Epub 2017 Dec 29.

Protein components of post-synaptic density lattice, a backbone structure for type I excitatory synapses.

Author information

1
Department of Neuroplasticity, Institute of Pathogenesis and Disease Prevention, Graduate School of Medicine, Shinshu University Academic Assembly, Matsumoto, Japan.
2
Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research Shinshu University, Matsumoto, Japan.
3
Department of Molecular and Cellular physiology, Shinshu University Academic Assembly, Institute of Medicine, Matsumoto, Japan.
4
Department of Instrumental Analysis, Research Center for Human and Environmental Science, Shinshu University, Matsumoto, Nagano, Japan.
5
Bio-X Institutes, Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
6
Distinguished Visiting Professor, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research Shinshu University, Matsumoto, Japan.

Abstract

It is essential to study the molecular architecture of post-synaptic density (PSD) to understand the molecular mechanism underlying the dynamic nature of PSD, one of the bases of synaptic plasticity. A well-known model for the architecture of PSD of type I excitatory synapses basically comprises of several scaffolding proteins (scaffold protein model). On the contrary, 'PSD lattice' observed through electron microscopy has been considered a basic backbone of type I PSDs. However, major constituents of the PSD lattice and the relationship between the PSD lattice and the scaffold protein model, remain unknown. We purified a PSD lattice fraction from the synaptic plasma membrane of rat forebrain. Protein components of the PSD lattice were examined through immuno-gold negative staining electron microscopy. The results indicated that tubulin, actin, α-internexin, and Ca2+ /calmodulin-dependent kinase II are major constituents of the PSD lattice, whereas scaffold proteins such as PSD-95, SAP102, GKAP, Shank1, and Homer, were rather minor components. A similar structure was also purified from the synaptic plasma membrane of forebrains from 7-day-old rats. On the basis of this study, we propose a 'PSD lattice-based dynamic nanocolumn' model for PSD molecular architecture, in which the scaffold protein model and the PSD lattice model are combined and an idea of dynamic nanocolumn PSD subdomain is also included. In the model, cytoskeletal proteins, in particular, tubulin, actin, and α-internexin, may play major roles in the construction of the PSD backbone and provide linker sites for various PSD scaffold protein complexes/subdomains.

KEYWORDS:

PSD lattice; molecular architecture; post-synaptic density; synaptic plasticity; type I synapse

PMID:
29134655
DOI:
10.1111/jnc.14254
[Indexed for MEDLINE]
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