Interaction between Teneurin-2 and microtubules via EB proteins provides a platform for GABAA receptor exocytosis
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 GABAA 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.
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Author details
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.
Reviewing Editor
- Kassandra M Ori-McKenney, University of California, United States
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) .
Version history
- Received: September 6, 2022
- Preprint posted: September 14, 2022 (view preprint)
- Accepted: June 3, 2023
- Accepted Manuscript published: June 5, 2023 (version 1)
- Version of Record published: June 21, 2023 (version 2)
Copyright
© 2023, Ichinose et al.
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.
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