Protein Kinase B/Akt1 Phosphorylates Dysbindin-1A at Serine 10 to Regulate Neuronal Development
Protein Kinase B/Akt1 Phosphorylates Dysbindin-1A at Serine 10 to Regulate Neuronal Development
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蛋白激酶 B/Akt1 在丝氨酸 10 处磷酸化 Dysbindin-1A，以调节神经元发育。
DOI：
10.1016/j.neuroscience.2022.01.025
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发表时间：
2022-03-21
期刊：
影响因子：
3.3
通讯作者：
Zhou, Tian
中科院分区：
文献类型：
--
作者：
Fei, Erkang;Chen, Peng;Zhou, Tian
精神分裂症是一种神经发育障碍，树突和树突棘功能障碍。Dysbindin-1是一种在精神分裂症患者大脑中减少的蛋白质，与树突和棘的发育有关。然而，目前尚不清楚dysbindin-1在神经元发育中的作用是如何调节的。在这里，我们发现蛋白激酶B/Akt 1，一种与精神分裂症有关的丝氨酸/苏氨酸激酶，在丝氨酸10（S10）磷酸化dysbindin-1A。dysbindin-1A的S10磷酸化在出生后神经元和突触发育阶段增加，并在突触后密度（PSD）富集。此外，过度表达dysbindin-1A的野生型或S10磷酸模拟突变体（S10 D），而不是S10磷酸死亡突变体（S10 A），挽救了dysbindin-1A敲低神经元中的树突和棘缺陷。这些结果表明Akt 1对dysbindin-1A的S10磷酸化是神经元发育所必需的，为dysbindin-1A在神经元发育中提供了潜在的调节机制。(C)2022 IBRO。由爱思唯尔有限公司出版。保留所有权利。
Schizophrenia is a neurodevelopmental disorder with dendrite and dendritic spine dysfunction. Dysbindin-1, a protein decreased in the brains of schizophrenia patients, is involved in the development of dendrites and spines. However, it is still unclear how the role of dysbindin-1 in neuronal development is regulated. Here, we showed protein kinase B/Akt1, a serineithreonine kinase implicated in schizophrenia, phosphorylated dysbindin-1A at serine 10 (S10). S10 phosphorylation of dysbindin-1A was increased during postnatal neuronal and synapse development stage, and was enriched in postsynaptic densities (PSDs). Furthermore, overexpressing wild type or S10 phospho-mimic mutant (S10D), but not S10 phospho-dead mutant (S10A) of dysbindin-1A rescued the dendrite and spine deficits in dysbindin-1A knockdown neurons. These results indicate S10 phosphorylation of dysbindin-1A by Akt1 is essential for neuronal development, providing a potential regulation mechanism for dysbindin-1A in neuronal development. (C) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.