Retinoic acid-induced protein 14 controls dendritic spine dynamics associated with depressive-like behaviors
- Pohang University of Science and Technology, Republic of Korea
Abstract
Dendritic spines are the central postsynaptic machinery that determines synaptic function. The F-actin within dendritic spines regulates their dynamic formation and elimination. Rai14 is an F‑actin-regulating protein with a membrane‑shaping function. Here, we identified the roles of Rai14 for the regulation of dendritic spine dynamics associated with stress-induced depressive-like behaviors. Rai14-deficient neurons exhibit reduced dendritic spine density in the Rai14+/- mouse brain, resulting in impaired functional synaptic activity. Rai14 was protected from degradation by complex formation with Tara, and accumulated in the dendritic spine neck, thereby enhancing spine maintenance. Concurrently, Rai14 deficiency in mice altered gene expression profile relevant to depressive conditions and increased depressive-like behaviors. Moreover, Rai14 expression was reduced in the prefrontal cortex of the mouse stress model, which was blocked by antidepressant treatment. Thus, we propose that Rai14-dependent regulation of dendritic spines may underlie the plastic changes of neuronal connections relevant to depressive-like behaviors.
Data availability
Source data files including the numerical data associated with the figures are provided (for figures 1, 2, 3, 4, and 5). The source data files with original uncropped western blot images are also provided as PDF files (figures with the uncropped gels with relevant band labelled) and a zipped folder (the original files of the raw unedited gels).Sequencing data have been deposited at Dryad (doi:10.5061/dryad.1rn8pk0w9)
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Data from: Retinoic acid-induced protein 14 controls dendritic spine dynamics associated with depressive-like behaviorsDryad Digital Repository, doi:10.5061/dryad.1rn8pk0w9.
Article and author information
Author details
Funding
National Research Foundation of Korea (NRF-2021R1A2C3010639)
- Sang Ki Park
National Research Foundation of Korea (NRF-2020M3E5E2039894)
- Sang Ki Park
National Research Foundation of Korea (NRF-2017R1A5A1015366)
- Sang Ki Park
Ministry of Science and ICT, South Korea (21-BR-03-01)
- Sang Ki Park
Ministry of Education (2020R1A6A3A01096024)
- Youngsik Woo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ryohei Yasuda, Max Planck Florida Institute for Neuroscience, United States
Ethics
Animal experimentation: All of the animals were handled according to approved Institutional Animal Care and Use Committee (IACUC) of Pohang University of Science and Technology (POSTECH-2017-0037, POSTECH-2019-0025, POSTECH-2020-0008, and POSTECH-2020-0018). All experiments were carried out under the approved guidelines.
Version history
- Received: February 9, 2022
- Preprint posted: February 22, 2022 (view preprint)
- Accepted: April 24, 2022
- Accepted Manuscript published: April 25, 2022 (version 1)
- Version of Record published: May 4, 2022 (version 2)
Copyright
© 2022, Kim 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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Retinoic acid-induced protein 14 controls dendritic spine dynamics associated with depressive-like behaviors
eLife 11:e77755.
https://doi.org/10.7554/eLife.77755
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