Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 34141, Republic of Korea.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
Cell Chem Biol. 2019 Dec 19;26(12):1652-1663.e4. doi: 10.1016/j.chembiol.2019.10.006. Epub 2019 Oct 30.
Actin waves are filamentous actin (F-actin)-rich structures that initiate in the somato-neuritic area and move toward neurite ends. The upstream cues that initiate actin waves are poorly understood. Here, using an optogenetic approach (Opto-cytTrkB), we found that local activation of the TrkB receptor around the neurite end initiates actin waves and triggers neurite elongation. During actin wave generation, locally activated TrkB signaling in the distal neurite was functionally connected with preferentially localized Rac1 and its signaling pathways in the proximal region. Moreover, TrkB activity changed the location of ankyrinG--the master organizer of the axonal initial segment-and initiated the stimulated neurite to acquire axonal characteristics. Taken together, these findings suggest that local Opto-cytTrkB activation switches the fate from minor to major axonal neurite during neuronal polarization by generating actin waves.
肌动蛋白波是富含丝状肌动蛋白（F-actin）的结构，它们起始于体神经元区域并向轴突末端移动。引发肌动蛋白波的上游线索还不太清楚。在这里，我们使用光遗传学方法（Opto-cytTrkB）发现，在轴突末端周围局部激活 TrkB 受体可以引发肌动蛋白波并触发轴突伸长。在肌动蛋白波产生过程中，远端轴突中局部激活的 TrkB 信号与优先定位在近端区域的 Rac1 及其信号通路在功能上相连。此外，TrkB 活性改变了锚蛋白 G 的位置——轴突起始段的主要组织者——并启动了受刺激的轴突获得轴突特征。总之，这些发现表明，通过产生肌动蛋白波，局部 Opto-cytTrkB 激活可以将神经元极化过程中较小的轴突分支命运转变为较大的轴突分支。
