摘要/Abstract
摘要： 目的·探究突触细胞黏附分子（synaptic cell adhesion molecule，sCAM）介导人类早期突触形成的信号通路。方法·从GEO数据库获取人类出生前前额叶皮层的单细胞测序数据，用伪时间排序模拟突触发生的基因表达过程。结合基因共表达分析和蛋白相互作用数据，构建蛋白相互作用网络，分析sCAM的相互作用分子和相关信号通路。结果·早期兴奋性神经元突触形成的基因表达过程可由单向的线性轨迹模拟。蛋白相互作用网络分析发现了sCAM 神经连接蛋白（neurexins）、神经配蛋白（neuroligins）以及LAR-型受体蛋白酪氨酸磷酸酶（LAR-type receptor-type protein tyrosine phosphatases，LAR-type RPTPs）的相互作用分子。Rho鸟苷交换因子-9（guanine nucleotide exchange factor 9，ARHGEF9）与neurexins、neuroligins发生相互作用，细胞分裂周期蛋白42（cell division cycle 42，CDC42）是网络的中心蛋白。淀粉样前体蛋白（amyloid precursor protein，APP）与neuroligins及neurexins的配体富亮氨酸重复序列跨膜蛋白3（leucine-rich repeat transmembrane neuronal protein 3，LRRTM3）发生相互作用。MAPK信号通路的成员丝裂原活化蛋白激酶8（mitogen-activated protein kinase 8，MAPK8）、双特异性磷酸酶4（dual specificity phosphatase 4，DUSP4）和CDC42参与LAR-type RPTPs的成员蛋白酪氨酸磷酸酶受体D（protein tyrosine phosphatase receptor type D，PTPRD）及其配体富亮氨酸重复和含纤连蛋白Ⅲ型结构域1（leucine rich repeat and fibronectin type Ⅲ domain containing 1，LRFN1）、LRFN2、LRFN5的相互作用网络。结论·生物信息学方法预测了重要sCAM neurexins、neuroligins和LAR-type RPTPs的相互作用蛋白和相关通路，可为实验研究提供有价值的参考。
关键词: 生物信息学, 突触发生, 神经发育, RNA测序, 突触细胞黏附分子, 蛋白相互作用
Abstract:
Objective · To investigate the signalling pathways mediatedsynaptic cell adhesion molecules (sCAMs) in the process of human prenatal synapse formation. Methods · The single-cell RNA-sequencing dataset of prenatal human prefrontal cortex was downloaded GEO (Gene Expression Omnibus) database. The gene dynamics was modelled with pseudotime ordering approach and the protein-protein interaction (PPI) network was constructedutilizing gene co- analysis and PPI database. The interacting molecules and associated pathways of sCAMs were explored. Results · The gene dynamics of early synapse formation in excitatory neurons can be modelled with linear trajectory. PPI network analysis identified the interacting molecules of neurexins, neuroligins, and LAR-type receptor-type protein tyrosine phosphatases (LAR-type RPTPs). Guanine nucleotide exchange factor 9 (ARHGEF9) interacted with neurexins and neuroligins, while cell division cycle 42 (CDC42) was the hub of the network. Amyloid precursor protein (APP) interacted with neuroligins and leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3), which is a ligand of neurexins. Finally, mitogen-activated protein kinase 8 (MAPK8), dual specificity phosphatase 4 (DUSP4), and CDC42, which participate MAPK signalling pathways, were involved in the PPI network of protein tyrosine phosphatase receptor type D (PTPRD, a member of LAR-type RPTPs) and its ligands leucine rich repeat and fibronectin type Ⅲ domain containing 1 (LRFN1), LRFN2, and LRFN5. Conclusion · Interacting proteins and associated pathways of neurexins, neuroligins, and LAR-type RPTPs can be predicted with bioinformatics methods, which may provide insights in experimental studies.
Key words: bioinformatics, synapse formation, neurodevelopment, RNA-sequencing, synaptic cell adhesion molecule (sCAM), protein-protein interaction
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