Department of Neurobiology and Behavior, State University of New York, Stony Brook 11794-5230, USA.
Neuron. 2011 Aug 11;71(3):433-46. doi: 10.1016/j.neuron.2011.06.041.
Semaphorin 3A (Sema3A) is a secreted factor known to guide axon/dendrite growth and neuronal migration. We found that it also acts as a polarizing factor for axon/dendrite development in cultured hippocampal neurons. Exposure of the undifferentiated neurite to localized Sema3A suppressed its differentiation into axon and promoted dendrite formation, resulting in axon formation away from the Sema3A source, and bath application of Sema3A to polarized neurons promoted dendrite growth but suppressed axon growth. Fluorescence resonance energy transfer (FRET) imaging showed that Sema3A elevated the cGMP but reduced cAMP and protein kinase A (PKA) activity, and its axon suppression is attributed to the downregulation of PKA-dependent phosphorylation of axon determinants LKB1 and GSK-3β. Downregulating Sema3A signaling in rat embryonic cortical progenitors via in utero electroporation of siRNAs against the Sema3A receptor neuropilin-1 also resulted in polarization defects in vivo. Thus, Sema3A regulates the earliest step of neuronal morphogenesis by polarizing axon/dendrite formation.
信号蛋白 Semaphorin 3A（Sema3A）是一种已知的可引导轴突/树突生长和神经元迁移的分泌因子。我们发现，它在培养的海马神经元中也是一种轴突/树突发育的极化因子。将未分化的神经突暴露于局部 Sema3A 下会抑制其分化为轴突，并促进树突形成，从而导致轴突远离 Sema3A 来源形成，而将 Sema3A 施加于极化神经元上会促进树突生长，但抑制轴突生长。荧光共振能量转移（FRET）成像显示，Sema3A 会升高 cGMP，但降低 cAMP 和蛋白激酶 A（PKA）活性，其对轴突的抑制作用归因于 PKA 依赖性下调轴突决定因素 LKB1 和 GSK-3β 的磷酸化。通过向大鼠胚胎皮质祖细胞中转染针对 Sema3A 受体神经纤毛蛋白-1 的 siRNA 进行体内电穿孔，也会导致体内的极化缺陷。因此，Sema3A 通过极化轴突/树突形成来调节神经元形态发生的最早步骤。
