Department of Biochemistry and Molecular Biophysics, New York, NY 10032, USA; Department of Systems Biology, New York, NY 10032, USA.
Department of Biochemistry and Molecular Biophysics, New York, NY 10032, USA.
Semin Cell Dev Biol. 2017 Sep;69:140-150. doi: 10.1016/j.semcdb.2017.07.023. Epub 2017 Jul 22.
Clustered protocadherins mediate neuronal self-recognition and non-self discrimination-neuronal "barcoding"-which underpin neuronal self-avoidance in vertebrate neurons. Recent structural, biophysical, computational, and cell-based studies on protocadherin structure and function have led to a compelling molecular model for the barcoding mechanism. Protocadherin isoforms assemble into promiscuous cis-dimeric recognition units and mediate cell-cell recognition through homophilic trans-interactions. Each recognition unit is composed of two arms extending from the membrane proximal EC6 domains. A cis-dimeric recognition unit with each arm coding adhesive trans homophilic specificity can generate a zipper-like assembly that in turn suggests a chain termination mechanism for self-vs-non-self-discrimination among vertebrate neurons.
聚集原钙黏蛋白介导神经元的自我识别和非自我识别——神经元的“条形码”——这是脊椎动物神经元中神经元自我回避的基础。最近对原钙黏蛋白结构和功能的结构、生物物理、计算和基于细胞的研究,为条形码机制提供了一个引人注目的分子模型。原钙黏蛋白同种型组装成混杂的顺式二聚体识别单元,并通过同型 trans 相互作用介导细胞间识别。每个识别单元由从膜近端 EC6 结构域延伸出的两个臂组成。一个具有每个臂编码黏附性 trans 同型特异性的顺式二聚体识别单元可以产生拉链状组装,这反过来又表明了脊椎动物神经元中自我与非自我识别的链终止机制。