Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Curr Opin Struct Biol. 2019 Feb;54:112-121. doi: 10.1016/j.sbi.2019.01.009. Epub 2019 Mar 2.
Neurexins constitute a large family of synaptic organizers. Their extracellular domains protrude into the synaptic cleft where they can form transsynaptic bridges with different partners. A unique constellation of structural elements within their ectodomains enables neurexins to create molecular platforms within the synaptic cleft that permit a large portfolio of partners to be recruited, assembled and their interactions to be dynamically regulated. Neurexins and their partners are implicated in neuropsychiatric diseases including autism spectrum disorder and schizophrenia. Detailed understanding of the mechanisms that underlie neurexin interactions may in future guide the design of tools to manipulate synaptic connections and their function, in particular those involved in the pathogenesis of neuropsychiatric disease.
神经连接蛋白构成了一个庞大的突触组织者家族。它们的细胞外结构域突出到突触间隙中,在那里可以与不同的伙伴形成跨突触桥。其细胞外结构域内独特的结构元素组合使神经连接蛋白能够在突触间隙内创建分子平台,从而允许大量的伙伴被招募、组装,并对它们的相互作用进行动态调节。神经连接蛋白及其伙伴与神经精神疾病有关,包括自闭症谱系障碍和精神分裂症。对神经连接蛋白相互作用的基础机制的深入了解,未来可能会指导设计用于操纵突触连接及其功能的工具,特别是那些与神经精神疾病发病机制相关的工具。