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标题：Drp1 SUMO/deSUMOylation by Senp5 isoforms influences ER tubulation and mitochondrial dynamics to regulate brain development
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作者：Seiya Yamada ; Ayaka Sato ; Naotada Ishihara 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：12
页码：1-31
DOI：10.1016/j.isci.2021.103484
语种：English
出版社：Elsevier
摘要：SummaryBrain development is a highly orchestrated process requiring spatiotemporally regulated mitochondrial dynamics. Drp1, a key molecule in the mitochondrial fission machinery, undergoes various post-translational modifications including conjugation to the small ubiquitin-like modifier (SUMO). However, the functional significance of SUMOylation/deSUMOylation on Drp1 remains controversial. SUMO-specific protease 5 (Senp5L) catalyzes the deSUMOylation of Drp1. We revealed that a splicing variant of Senp5L, Senp5S, which lacks peptidase activity, prevents deSUMOylation of Drp1 by competing against other Senps. The altered SUMOylation level of Drp1 induced by Senp5L/5S affects mitochondrial morphology probably through controlling Drp1 ubiquitination and tubulation of the endoplasmic reticulum. A dynamic SUMOylation/deSUMOylation balance controls neuronal polarization and migration during the development of the cerebral cortex. These findings suggest a novel role of post-translational modification, in which deSUMOylation enzyme isoforms competitively regulate mitochondrial dynamics via Drp1 SUMOylation levels, in a tightly controlled process of neuronal differentiation and corticogenesis.Graphical abstractDisplay OmittedHighlights•We identified the novel peptidase-activity lacking splice valiant of Senp5, or Senp5S•The conventional Senp5 (Senp5L) and Senp5S competitively regulate target SUMOylation•Senp5L/S inhibits/promotes mitochondrial fission via the control of Drp1 SUMOylation•Balanced expression of Senp5L/S and Drp1 SUMOylation are required for corticogenesisCellular neuroscience; Molecular neuroscience; Molecular physiology