Laboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université Catholique de Louvain, 1200 Brussels, Belgium.
Biomolecules. 2020 Jun 26;10(6):964. doi: 10.3390/biom10060964.
During embryonic development and adulthood, Reelin exerts several important functions in the brain including the regulation of neuronal migration, dendritic growth and branching, dendritic spine formation, synaptogenesis and synaptic plasticity. As a consequence, the Reelin signaling pathway has been associated with several human brain disorders such as lissencephaly, autism, schizophrenia, bipolar disorder, depression, mental retardation, Alzheimer's disease and epilepsy. Several elements of the signaling pathway are known. Core components, such as the Reelin receptors very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2), Src family kinases Src and Fyn, and the intracellular adaptor Disabled-1 (Dab1), are common to most but not all Reelin functions. Other downstream effectors are, on the other hand, more specific to defined tasks. Reelin is a large extracellular protein, and some aspects of the signal are regulated by its processing into smaller fragments. Rather than being inhibitory, the processing at two major sites seems to be fulfilling important physiological functions. In this review, I describe the various cellular events regulated by Reelin and attempt to explain the current knowledge on the mechanisms of action. After discussing the shared and distinct elements of the Reelin signaling pathway involved in neuronal migration, dendritic growth, spine development and synaptic plasticity, I briefly outline the data revealing the importance of Reelin in human brain disorders.
在胚胎发育和成年期， Reelin 在大脑中发挥着几种重要功能，包括调节神经元迁移、树突生长和分支、树突棘形成、突触发生和突触可塑性。因此， Reelin 信号通路与几种人类大脑疾病有关，如无脑回畸形、自闭症、精神分裂症、双相情感障碍、抑郁症、智力迟钝、阿尔茨海默病和癫痫。该信号通路的几个元素是已知的。核心成分，如 Reelin 受体极低密度脂蛋白受体（VLDLR）和载脂蛋白 E 受体 2（ApoER2）、Src 家族激酶Src 和 Fyn，以及细胞内衔接蛋白Disabled-1（Dab1），是大多数但不是所有 Reelin 功能所共有的。另一方面，其他下游效应物则更为特定于特定任务。 Reelin 是一种大型细胞外蛋白，其信号的某些方面受其加工成较小片段的调节。这种加工似乎在两个主要位点发挥着重要的生理功能，而不是抑制性的。在这篇综述中，我描述了 Reelin 调节的各种细胞事件，并试图解释其作用机制的现有知识。在讨论了参与神经元迁移、树突生长、棘突发育和突触可塑性的 Reelin 信号通路的共享和独特元素之后，我简要概述了揭示 Reelin 在人类大脑疾病中的重要性的数据。
