Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits.
Subcellular sorting of neuregulins controls the assembly of excitatory-inhibitory cortical circuits.
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作者：
Exposito-Alonso D;Osório C;Bernard C;Pascual-García S;Del Pino I;Marín O;Rico B
特定神经元回路的组装依赖于突触前和突触后神经元中互补分子程序的表达。在大脑皮层中，酪氨酸激酶受体ErbB4对gaba能中间神经元的特定群体的连接至关重要，在这种情况下，它既调节抑制性突触的形成，也调节这些细胞接收的兴奋性突触的发育。在这里，我们发现Nrg1和Nrg3是神经调节蛋白营养因子家族的两个成员，分别调节小鼠大脑皮层中间神经元的抑制性输出和兴奋性输入。Nrg1和Nrg3在这一过程中的不同作用不是由于它们与受体结合的egf样结构域，而是由于它们在锥体细胞内独特的亚细胞定位。我们的研究揭示了一种新的皮层回路组装策略，该策略涉及与家族相关的突触蛋白的差异亚细胞分选。
The assembly of specific neuronal circuits relies on the expression of complementary molecular programs in presynaptic and postsynaptic neurons. In the cerebral cortex, the tyrosine kinase receptor ErbB4 is critical for the wiring of specific populations of GABAergic interneurons, in which it paradoxically regulates both the formation of inhibitory synapses as well as the development of excitatory synapses received by these cells. Here, we found that Nrg1 and Nrg3, two members of the neuregulin family of trophic factors, regulate the inhibitory outputs and excitatory inputs of interneurons in the mouse cerebral cortex, respectively. The differential role of Nrg1 and Nrg3 in this process is not due to their receptor-binding EGF-like domain, but rather to their distinctive subcellular localization within pyramidal cells. Our study reveals a novel strategy for the assembly of cortical circuits that involves the differential subcellular sorting of family-related synaptic proteins.