European Molecular Biology Laboratory, Meyerhofstraße 1, 69012 Heidelberg, Germany; Centre for Organismal Studies, Heidelberg University, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.
Curr Biol. 2020 May 18;30(10):R603-R616. doi: 10.1016/j.cub.2020.04.008.
Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.
神经元是高度特化的细胞，配备有复杂的分子机制，用于接收、整合、传导和分配信息。神经元的进化起源仍然未得到解决。新的和现有的蛋白质是如何组装成突触的复杂机制以及沿着神经元传导电流的装置的？在这篇综述中，神经元进化中功能性模块的逐步组装为多细胞生物中细胞类型的分子机制的出现和修饰提供了范例。突触前机制是通过钙调节的大囊泡释放的修饰而出现的，而突触后机制则有不同的起源：谷氨酸能突触起源于感觉信号模块和丝状伪足生长模块的融合，而 GABA 能突触则整合了一个古老的肌动蛋白调节模块。突触连接反过来又围绕两个受磷酸化控制的粘附模块构建，这些模块类似于隔膜和粘附连接。最后，神经元动作电位通过一系列电压门控离子通道的复制和修饰而出现。基于这些起源，确定了导致动物进化中第一个神经元诞生的关键分子创新。
