Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Daisuke Murata
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Takashi Kato
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Tatsuya Yamada
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Yoichi Araki
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
Atsushi Saito
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Yoshihiro Adachi
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Atsushi Igarashi
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Shuo Li
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
Mikhail Pletnikov
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Richard L Huganir
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
Shigeki Watanabe
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
Atsushi Kamiya
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Miho Iijima
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
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.
