Desprez Florence, Ung Dévina C, Vourc'h Patrick, Jeanne Médéric, Laumonnier Frédéric
UMR1253, iBrain, Inserm, University of Tours, Tours, France.
Service de Génétique, Centre Hospitalier Régional Universitaire, Tours, France.
Front Neurosci. 2023 Apr 17;17:1154446. doi: 10.3389/fnins.2023.1154446. eCollection 2023.
The dihydropyrimidinase-like (DPYSL) proteins, also designated as the collapsin response mediators (CRMP) proteins, constitute a family of five cytosolic phosphoproteins abundantly expressed in the developing nervous system but down-regulated in the adult mouse brain. The DPYSL proteins were initially identified as effectors of semaphorin 3A (Sema3A) signaling and consequently involved in regulation of growth cone collapse in young developing neurons. To date, it has been established that DPYSL proteins mediate signals for numerous intracellular/extracellular pathways and play major roles in variety of cellular process including cell migration, neurite extension, axonal guidance, dendritic spine development and synaptic plasticity through their phosphorylation status. The roles of DPYSL proteins at early stages of brain development have been described in the past years, particularly for DPYSL2 and DPYSL5 proteins. The recent characterization of pathogenic genetic variants in and in human genes associated with intellectual disability and brain malformations, such as agenesis of the corpus callosum and cerebellar dysplasia, highlighted the pivotal role of these actors in the fundamental processes of brain formation and organization. In this review, we sought to establish a detailed update on the knowledge regarding the functions of genes and proteins in brain and to highlight their involvement in synaptic processing in later stages of neurodevelopment, as well as their particular contribution in human neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASD) and intellectual disability (ID).
二氢嘧啶酶样（DPYSL）蛋白，也被称为塌陷反应介导蛋白（CRMP），由五种胞质磷蛋白组成，在发育中的神经系统中大量表达，但在成年小鼠大脑中表达下调。DPYSL蛋白最初被鉴定为信号素3A（Sema3A）信号的效应器，因此参与调控幼龄发育神经元生长锥的塌陷。迄今为止，已经证实DPYSL蛋白介导众多细胞内/细胞外信号通路，并通过其磷酸化状态在多种细胞过程中发挥主要作用，包括细胞迁移、神经突延伸、轴突导向、树突棘发育和突触可塑性。过去几年已经描述了DPYSL蛋白在脑发育早期阶段的作用，特别是DPYSL2和DPYSL5蛋白。最近对与智力残疾和脑畸形相关的人类基因中的致病遗传变异的表征，如胼胝体发育不全和小脑发育异常，突出了这些因子在脑形成和组织的基本过程中的关键作用。在本综述中，我们试图详细更新关于这些基因和蛋白在脑中功能的知识，并强调它们在神经发育后期阶段参与突触加工，以及它们在人类神经发育障碍（NDD），如自闭症谱系障碍（ASD）和智力残疾（ID）中的特殊贡献。
