Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division

Itoh, Murata, Kato, Yamada, Araki, Saito, Adachi, Igarashi, Li, Pletnikov, Huganir, Watanabe, Kamiya, Iijima, Sesaki (2019) Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division Elife (IF: 7.7) 8

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.© 2019, Itoh et al.

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824841
http://www.ncbi.nlm.nih.gov/pubmed/31603426
http://dx.doi.org/10.7554/eLife.44739

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