Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation
Developmental dynamics of the postsynaptic proteome to understand synaptic maturation and dysmaturation
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DOI：
10.1101/2022.05.05.490828
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发表时间：
2022-05
期刊：
影响因子：
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通讯作者：
T. Kaizuka;Takehiro Suzuki;Noriyuki Kishi;M. Kilimann;T. Ueyama;Masahiko Watanabe;Hideyuki Okano
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文献类型：
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作者：
T. Kaizuka;Takehiro Suzuki;Noriyuki Kishi;M. Kilimann;T. Ueyama;Masahiko Watanabe;Hideyuki Okano
突触后密度是由兴奋性突触的突触后膜下的∼-1,000蛋白组成的蛋白质凝聚体。突触的数量、形状和可塑性在发育过程中会发生变化。然而，突触蛋白在发育过程中的动态变化还没有被完全了解。在这里，我们展示了在发育过程中小鼠和灵长类动物大脑中PSD蛋白组成的变化。参与突触调节的蛋白质在2周大的小鼠PSD上的差异表达(288个减少，267个增加)中得到丰富。我们发现，小鼠大脑中PSD蛋白丰度的变化与出生后小鼠和围产期灵长类动物的基因表达水平有关。这种PSD成分的改变很可能在小鼠模型或自闭症谱系障碍(ASD)患者的大脑中存在缺陷。最后，我们证明了普通绒猴(Callithrix Jacchus)的大脑在幼年后改变了PSD的组成。2个月龄后PSD成分的变化与小鼠不同。我们的结果提供了PSD成分在发育过程中重塑的全面架构，这可能解释突触成熟的分子基础和精神障碍(如ASD)的病理。
The postsynaptic density (PSD) is a protein condensate composed of ∼1,000 proteins beneath the postsynaptic membrane of excitatory synapses. The number, shape, and plasticity of synapses are altered during development. However, the dynamics of synaptic protein composition across development have not been fully understood. Here we show alterations of PSD protein composition in mouse and primate brains during development. Proteins involved in synapse regulation are enriched in the differentially expressed (288 decreased and 267 increased) proteins on mouse PSD after a 2-week-old. We find that the changes in PSD protein abundance in mouse brains correlate with gene expression levels in postnatal mice and perinatal primates. This alteration of PSD composition is likely to be defective in the brains of mouse models or patients with autism spectrum disorder (ASD). Finally, we demonstrate that the brain of the common marmoset (Callithrix jacchus) changes PSD composition after the juvenile period. The alteration of PSD composition after 2-month-old is distinct from that observed in mice. Our results provide a comprehensive architecture of the remodeling of PSD composition across development, which may explain the molecular basics of synapse maturation and the pathology of psychiatric disorders, such as ASD.