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Gbb 谷胱甘肽化促进其蛋白酶体介导的降解，从而抑制突触生长。

Gbb glutathionylation promotes its proteasome-mediated degradation to inhibit synapse growth.

机构信息

Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences , Beijing, China.

University of Chinese Academy of Sciences , Beijing, China.

出版信息

J Cell Biol. 2023 Sep 4;222(9). doi: 10.1083/jcb.202202068. Epub 2023 Jun 30.

DOI:10.1083/jcb.202202068
PMID:37389657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10316630/
Abstract

Glutathionylation is a posttranslational modification involved in various molecular and cellular processes. However, it remains unknown whether and how glutathionylation regulates nervous system development. To identify critical regulators of synapse growth and development, we performed an RNAi screen and found that postsynaptic knockdown of glutathione transferase omega 1 (GstO1) caused significantly more synaptic boutons at the Drosophila neuromuscular junctions. Genetic and biochemical analysis revealed an increased level of glass boat bottom (Gbb), the Drosophila homolog of mammalian bone morphogenetic protein (BMP), in GstO1 mutants. Further experiments showed that GstO1 is a critical regulator of Gbb glutathionylation at cysteines 354 and 420, which promoted its degradation via the proteasome pathway. Moreover, the E3 ligase Ctrip negatively regulated the Gbb protein level by preferentially binding to glutathionylated Gbb. These results unveil a novel regulatory mechanism in which glutathionylation of Gbb facilitates its ubiquitin-mediated degradation. Taken together, our findings shed new light on the crosstalk between glutathionylation and ubiquitination of Gbb in synapse development.

摘要

谷胱甘肽化是一种参与各种分子和细胞过程的翻译后修饰。然而，谷胱甘肽化是否以及如何调节神经系统的发育仍不清楚。为了鉴定参与突触生长和发育的关键调控因子，我们进行了 RNAi 筛选，发现谷胱甘肽转移酶 ω1（GstO1）在后突触中的敲低导致果蝇肌神经接点处的突触末梢明显增多。遗传和生化分析显示，GstO1 突变体中果蝇同源物玻璃船底（Gbb）的水平升高，哺乳动物骨形态发生蛋白（BMP）的同源物。进一步的实验表明，GstO1 是 Gbb 半胱氨酸 354 和 420 上谷胱甘肽化的关键调控因子，通过蛋白酶体途径促进其降解。此外，E3 连接酶 Ctrip 通过优先结合谷胱甘肽化的 Gbb 来负调控 Gbb 蛋白水平。这些结果揭示了一种新的调控机制，即 Gbb 的谷胱甘肽化促进其泛素介导的降解。总之，我们的发现揭示了谷胱甘肽化和泛素化在突触发育中的 Gbb 相互作用的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/58c89d570c5d/JCB_202202068_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/0e8a4105e4f8/JCB_202202068_Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/e3cab24d9f3a/JCB_202202068_Fig4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/462919162c3e/JCB_202202068_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/4ee06c242250/JCB_202202068_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/58c89d570c5d/JCB_202202068_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/0e8a4105e4f8/JCB_202202068_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/5f169bd2c4f6/JCB_202202068_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/9503c83daca6/JCB_202202068_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/f0a900b720f9/JCB_202202068_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/e3cab24d9f3a/JCB_202202068_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/e494ff5b3533/JCB_202202068_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/e6865b6eff6b/JCB_202202068_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/1ebc392df100/JCB_202202068_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/0cf371070bf7/JCB_202202068_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/51ce96f60112/JCB_202202068_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/466938491676/JCB_202202068_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/462919162c3e/JCB_202202068_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/4ee06c242250/JCB_202202068_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/231b/10316630/58c89d570c5d/JCB_202202068_Fig10.jpg

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