美国加州大学Arnold R. Kriegstein、Arnold R. Kriegstein研究组取得一项新突破。他们的最新研究利用跨物种蛋白质组学图谱揭示了人类突触发育的新特征。这一研究成果于2023年9月13日发表在国际学术期刊《自然》上。

研究人员揭示了人、猕猴和小鼠新皮层中突触发育的跨物种蛋白质组学图谱。通过跟踪1000多种突触后密度（PSD）蛋白从妊娠中期到成年早期的变化，研究发现人PSD成熟可分为三个主要阶段，这些阶段由不同的调控途径主导。跨物种比较表明，人类PSD的成熟速度比其他物种慢两到三倍，并且在围产期含有更高的Rho鸟嘌呤核苷酸交换因子（RhoGEFs）。人类神经元中RhoGEF信号传导增强导致树突棘形态发育和突触功能完善的延迟，可能是人类大脑发育的新特征。

此外，PSD蛋白可分为四个模块，发挥阶段和细胞类型特异性功能，这可能解释了它们与认知功能和疾病的差异关联。该研究揭示的突触发育蛋白质组学图谱为研究突触成熟的分子基础和进化变化提供了参考。

据悉，对突触发育过程的分子机制和进化变化仍然知之甚少。

附：英文原文

Title: A cross-species proteomic map reveals neoteny of human synapse development

Author: Wang, Li, Pang, Kaifang, Zhou, Li, Cebrin-Silla, Arantxa, Gonzlez-Granero, Susana, Wang, Shaohui, Bi, Qiuli, White, Matthew L., Ho, Brandon, Li, Jiani, Li, Tao, Perez, Yonatan, Huang, Eric J., Winkler, Ethan A., Paredes, Mercedes F., Kovner, Rothem, Sestan, Nenad, Pollen, Alex A., Liu, Pengyuan, Li, Jingjing, Piao, Xianhua, Garca-Verdugo, Jos Manuel, Alvarez-Buylla, Arturo, Liu, Zhandong, Kriegstein, Arnold R.

Issue&Volume: 2023-09-13

Abstract: The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood1,2. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell-type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation. A study presents a cross-species proteomic map of synapse development in neocortex and reveals that the human postsynaptic density assembly develops two to three times slower than that in macaques and mice.

DOI: 10.1038/s41586-023-06542-2

Source: https://www.nature.com/articles/s41586-023-06542-2