Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, 60611, IL, USA; Instituto Universitario de Investigación en Neuroquímica, Department of Biochemistry and Molecular Biology, School of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, 60611, IL, USA.
Trends Neurosci. 2022 Jun;45(6):483-498. doi: 10.1016/j.tins.2022.03.004. Epub 2022 Apr 13.
Ectodomain shedding (ES) is a post-translational protein modification process that plays key roles in health and disease. Many neuronal and synaptic membrane proteins are known to undergo ES, but the complexity of functions regulated by the shed peptides is only beginning to be unraveled. Here, we provide an overview of emerging evidence demonstrating that synaptic ES can mediate autocrine and paracrine signaling. We also discuss how advances in large-scale proteomic analyses are leading to the identification of novel synaptic proteins undergoing ES, as well as the targets and functions of their soluble ectodomains. Finally, we provide an overview of how cerebrospinal fluid (CSF) analyses of shed proteins could be used as a potential source of new biomarkers for neuropsychiatric disorders.
细胞外结构域脱落（ES）是一种翻译后蛋白修饰过程，在健康和疾病中发挥着关键作用。许多神经元和突触膜蛋白都被发现经历了 ES，但由脱落肽调节的功能的复杂性才刚刚开始被揭示。在这里，我们提供了一个概述，展示了新兴的证据表明突触 ES 可以介导自分泌和旁分泌信号。我们还讨论了大规模蛋白质组分析的进展如何导致识别经历 ES 的新型突触蛋白，以及它们的可溶性细胞外结构域的靶标和功能。最后，我们概述了如何分析脑脊液中脱落蛋白作为神经精神疾病新生物标志物的潜在来源。
