Laboratorio de Neurobiología, Department of Biomedicine, Universidad de Antofagasta, Avenida Angamos 601, 1270300, Antofagasta, Chile.
Cell Mol Life Sci. 2010 Jun;67(11):1751-4. doi: 10.1007/s00018-010-0343-5. Epub 2010 Mar 25.
Presynaptic differentiation takes place over three interrelated acts involving the biogenesis and trafficking of molecular complexes of active zone material, the "trapping" or stabilization of active zone sites, and the subsequent development of mature synapses. Although the identities of proteins involved with establishing presynaptic specializations have been increasingly delineated, the exact functional mechanisms by which the active zone is assembled remain poorly understood. Here, we discuss a theoretical model for how the trapping stage of presynaptic differentiation might occur in developing neurons. We suggest that subsets of active zone proteins containing polyglutamine domains undergo concentration-dependent prion-like conversions as they accumulate at the plasma membrane. This conversion might serve to aggregate the proteins into a singular structure, which is then able to recruit scaffolding agents necessary for regulated synaptic transmission. A brief informatics analysis in support of this 'Q' assembly hypothesis--across commonly used models of synaptogenesis--is presented.
突触前分化发生在三个相互关联的过程中，涉及活性区物质分子复合物的生物发生和运输、“捕获”或稳定活性区部位，以及随后成熟突触的发育。尽管与建立突触前特化相关的蛋白质的身份已逐渐被阐明，但活性区组装的确切功能机制仍知之甚少。在这里，我们讨论了一个关于突触前分化的捕获阶段如何在发育中的神经元中发生的理论模型。我们认为，含有多谷氨酰胺结构域的活性区蛋白亚基在积累到质膜时会发生浓度依赖性的类朊病毒转换。这种转换可能将蛋白质聚集到一个单一的结构中，然后能够招募调节突触传递所必需的支架蛋白。我们提出了一个简短的信息学分析来支持这个“Q”组装假说——跨越常用的突触发生模型。
