From the Secció Zoologia i Antropologia Biològica, Dept Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Spain (Soler, Fañanás, Fatjó-Vilas); the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain (Soler, Fañanás, Parellada, Fatjó-Vilas); Servicio de Psiquiatría del Niño y del Adolescente, Hospital General Universitario Gregorio Marañón, Madrid, Spain, Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IiSGM), Departamento de Psiquiatría, Facultad de Medicina, Universidad Complutense, Madrid, Spain (Parellada); the Centre Hospitalier Sainte-Anne, Service Hospitalo-Universitaire, Faculté de Médecine Paris Descartes, Paris, France (Krebs); the Université Paris Descartes, Inserm Centre de Psychiatrie et Neurosciences, Laboratoire de Physiopathologie des Maladies Psychiatriques, Paris, France (Krebs); the CNRS, GDR 3557, Institut de Psychiatrie, Paris, France (Krebs); the Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, QC (Rouleau); and the FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain (Fatjó-Vilas).
J Psychiatry Neurosci. 2018 Jul;43(4):223-244. doi: 10.1503/jpn.170066.
Scaffolding proteins represent an evolutionary solution to controlling the specificity of information transfer in intracellular networks. They are highly concentrated in complexes located in specific subcellular locations. One of these complexes is the postsynaptic density of the excitatory synapses. There, scaffolding proteins regulate various processes related to synaptic plasticity, such as glutamate receptor trafficking and signalling, and dendritic structure and function. Most scaffolding proteins can be grouped into 4 main families: discs large (DLG), discs-large-associated protein (DLGAP), Shank and Homer. Owing to the importance of scaffolding proteins in postsynaptic density architecture, it is not surprising that variants in the genes that code for these proteins have been associated with neuropsychiatric diagnoses, including schizophrenia and autism-spectrum disorders. Such evidence, together with the clinical, neurobiological and genetic overlap described between schizophrenia and autism-spectrum disorders, suggest that alteration of scaffolding protein dynamics could be part of the pathophysiology of both. However, despite the potential importance of scaffolding proteins in these psychiatric conditions, no systematic review has integrated the genetic and molecular data from studies conducted in the last decade. This review has the following goals: to systematically analyze the literature in which common and/or rare genetic variants (single nucleotide polymorphisms, single nucleotide variants and copy number variants) in the scaffolding family genes are associated with the risk for either schizophrenia or autism-spectrum disorders; to explore the implications of the reported genetic variants for gene expression and/or protein function; and to discuss the relationship of these genetic variants to the shared genetic, clinical and cognitive traits of schizophrenia and autism-spectrum disorders.
支架蛋白是一种进化解决方案，可控制细胞内网络中信息传递的特异性。它们高度集中在位于特定亚细胞位置的复合物中。其中一种复合物是兴奋性突触的突触后密度。在那里，支架蛋白调节与突触可塑性相关的各种过程，例如谷氨酸受体运输和信号转导，以及树突结构和功能。大多数支架蛋白可以分为 4 个主要家族：Discs large (DLG)、Discs-large-associated protein (DLGAP)、Shank 和 Homer。由于支架蛋白在突触后密度结构中的重要性，编码这些蛋白质的基因中的变异与神经精神诊断（包括精神分裂症和自闭症谱系障碍）相关并不奇怪。这种证据，以及精神分裂症和自闭症谱系障碍之间描述的临床、神经生物学和遗传重叠，表明支架蛋白动力学的改变可能是这两种疾病病理生理学的一部分。然而，尽管支架蛋白在这些精神疾病中的潜在重要性，过去十年中进行的研究的遗传和分子数据尚未得到系统的综述。本综述有以下目标：系统分析文献，其中常见和/或罕见遗传变异（单核苷酸多态性、单核苷酸变异和拷贝数变异）与精神分裂症或自闭症谱系障碍的风险相关；探讨报告的遗传变异对基因表达和/或蛋白质功能的影响；并讨论这些遗传变异与精神分裂症和自闭症谱系障碍的共同遗传、临床和认知特征的关系。
