期刊
ISCIENCE
卷 24, 期 12, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.103484
关键词
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资金
- Japan Society for the Promotion of Science [18K06491, 26430042]
- Waseda University [2018K-352, 2015K-249, 2017K-301]
- Grants-in-Aid for Scientific Research [18K06491, 26430042] Funding Source: KAKEN
The development of the brain requires a dynamic balance of SUMOylation/deSUMOylation to control neuronal polarization and migration, with the impact of Drp1 on mitochondrial morphology and endoplasmic reticulum controlled by Senp5L/5S competitively.
Brain 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.
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