TY - JOUR TI - Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division AU - Itoh, Kie AU - Murata, Daisuke AU - Kato, Takashi AU - Yamada, Tatsuya AU - Araki, Yoichi AU - Saito, Atsushi AU - Adachi, Yoshihiro AU - Igarashi, Atsushi AU - Li, Shuo AU - Pletnikov, Mikhail AU - Huganir, Richard L AU - Watanabe, Shigeki AU - Kamiya, Atsushi AU - Iijima, Miho AU - Sesaki, Hiromi A2 - Robinson, Margaret S A2 - Stainier, Didier Y A2 - Perrais, David A2 - Lobo, Mary Kay VL - 8 PY - 2019 DA - 2019/10/11 SP - e44739 C1 - eLife 2019;8:e44739 DO - 10.7554/eLife.44739 UR - https://doi.org/10.7554/eLife.44739 AB - 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. KW - Drp1 KW - endocytosis KW - brain KW - mitochondria JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -