Interaction between Teneurin-2 and microtubules via EB proteins provides a platform for GABAA receptor exocytosis

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Abstract

Neurons form dense neural circuits by connecting to each other via synapses and exchange information through synaptic receptors to sustain brain activities. Excitatory postsynapses form and mature on spines composed predominantly of actin, while inhibitory synapses are formed directly on the shafts of dendrites where both actin and microtubules (MTs) are present. Thus, it is the accumulation of specific proteins that characterizes inhibitory synapses. In this study, we explored the mechanisms that enable efficient protein accumulation at inhibitory postsynapse. We found that some inhibitory synapses function to recruit the plus end of MTs. One of the synaptic organizers, Teneurin-2 (TEN2), tends to localize to such MT-rich synapses and recruits MTs to inhibitory postsynapses via interaction with MT plus-end tracking proteins EBs. This recruitment mechanism provides a platform for the exocytosis of GABA_A receptors. These regulatory mechanisms could lead to a better understanding of the pathogenesis of disorders such as schizophrenia and autism, which are caused by excitatory/inhibitory (E/I) imbalances during synaptogenesis.

Data availability

Excel files are attached as source files.

The following previously published data sets were used

1. Loh KH
2. et al
(2016) Table S1. Excitatory and Inhibitory Synaptic Cleft Proteomes.
CellPress.

https://doi.org/10.1016/j.cell.2016.07.041

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Author details

Sotaro Ichinose

Department of Anatomy, Gunma University, Gunma, Japan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1470-2957
Yoshihiro Susuki

Department of Anatomy, Gunma University, Gunma, Japan

Competing interests
The authors declare that no competing interests exist.
Nobutake Hosoi

Department of Neurophysiology and Neural Repair, Gunma University, Gunma, Japan

Competing interests
The authors declare that no competing interests exist.
Ryosuke Kaneko

Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

Competing interests
The authors declare that no competing interests exist.
Mizuho Ebihara

Department of Anatomy, Gunma University, Gunma, Japan

Competing interests
The authors declare that no competing interests exist.
Hirokazu Hirai

Department of Neurophysiology and Neural Repair, Gunma University, Maebashi, Japan

Competing interests
The authors declare that no competing interests exist.
Hirohide Iwasaki

Department of Anatomy, Gunma University, Gunma, Japan

For correspondence
h-iwasaki@gunma-u.ac.jp

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7432-5938

Funding

Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (C) 18K06499)

Hirohide Iwasaki

Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research (C) 22K06805)

Hirohide Iwasaki

Takeda Foundation (Medical Research Grants)

Hirohide Iwasaki

Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientist)

Sotaro Ichinose

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The experiments in this study have passed a rigorous ethical review and have been approved by Gunma University for animal experiments (approval number: 20-061) .

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.