Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division
- Johns Hopkins University School of Medicine, United States
Abstract
Dynamin-related protein 1 (Drp1) divides mitochondria as a mechano-chemical GTPase. However, the function of Drp1 beyond mitochondrial division is largely unknown. Multiple Drp1 isoforms are produced through mRNA splicing. One such isoform, Drp1ABCD, contains all four alternative exons and is specifically expressed in the brain. Here, we studied the function of Drp1ABCD in mouse neurons in both culture and animal systems using isoform-specific knockdown by shRNA and isoform-specific knockout by CRISPR/Cas9. We found that the expression of Drp1ABCD is induced during postnatal brain development. Drp1ABCD is enriched in dendritic spines and regulates postsynaptic clathrin-mediated endocytosis by positioning the endocytic zone at the postsynaptic density, independently of mitochondrial division. Drp1ABCD loss promotes the formation of ectopic dendrites in neurons and enhanced sensorimotor gating behavior in mice. These data reveal that Drp1ABCD controls postsynaptic endocytosis, neuronal morphology and brain function.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (GM131768)
- Miho Iijima
National Institute of General Medical Sciences (GM123266)
- Hiromi Sesaki
National Institute of General Medical Sciences (GM130695)
- Hiromi Sesaki
National Institute on Drug Abuse (DA041208)
- Mikhail Pletnikov
- Atsushi Kamiya
National Institute of Mental Health (MH083728)
- Mikhail Pletnikov
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal work was conducted according to the guidelines established by the Johns Hopkins University Committee on Animal Care and Use. The protocol (MO17M181) has been approved by the same committee.
Reviewing Editor
- Margaret S Robinson, University of Cambridge, United Kingdom
Publication history
- Received: December 27, 2018
- Accepted: October 10, 2019
- Accepted Manuscript published: October 11, 2019 (version 1)
- Accepted Manuscript updated: October 16, 2019 (version 2)
- Version of Record published: November 1, 2019 (version 3)
Copyright
© 2019, Itoh 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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Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division
eLife 8:e44739.
https://doi.org/10.7554/eLife.44739
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