Fei Erkang, Chen Peng, Zhang Qian, Zhong Yanzi, Zhou Tian
Laboratory of Synaptic Development and Plasticity, Institute of Life Science, Nanchang University, Nanchang 330031, China.
School of Basic Medical Sciences, Nanchang University, Nanchang 330031, China.
Neuroscience. 2022 May 10;490:66-78. doi: 10.1016/j.neuroscience.2022.01.025. Epub 2022 Feb 3.
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 serine/threonine 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.
精神分裂症是一种伴有树突和树突棘功能障碍的神经发育障碍疾病。失调结合蛋白-1是一种在精神分裂症患者大脑中含量降低的蛋白质，它参与树突和树突棘的发育。然而，失调结合蛋白-1在神经元发育中的作用是如何被调控的仍不清楚。在此，我们发现蛋白激酶B/Akt1（一种与精神分裂症有关的丝氨酸/苏氨酸激酶）可使失调结合蛋白-1A在丝氨酸10（S10）位点发生磷酸化。失调结合蛋白-1A的S10磷酸化在出生后神经元和突触发育阶段增加，并在突触后致密物（PSD）中富集。此外，过表达失调结合蛋白-1A的野生型或S10磷酸化模拟突变体（S10D），而不是S10磷酸化失活突变体（S10A），可挽救失调结合蛋白-1A敲低神经元中的树突和树突棘缺陷。这些结果表明，Akt1介导的失调结合蛋白-1A的S10磷酸化对神经元发育至关重要，为失调结合蛋白-1A在神经元发育中提供了一种潜在的调控机制。
