Chou Vivian T, Johnson Seth, Long Jennifer, Vounatsos Maxime, Van Vactor David
Department of Cell Biology and Program in Neuroscience, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.
Cytoskeleton (Hoboken). 2020 Jan;77(1-2):4-15. doi: 10.1002/cm.21578. Epub 2019 Nov 21.
Regulation of the synaptic cytoskeleton is essential to proper neuronal development and wiring. Perturbations in neuronal microtubules (MTs) are associated with numerous pathologies, yet it remains unclear how changes in MTs may be coupled to synapse morphogenesis. Studies have identified many MT regulators that promote synapse growth. However, less is known about the factors that restrict growth, despite the potential links of synaptic overgrowth to severe neurological conditions. Here, we report that dTACC, which is implicated in MT assembly and stability, prevents synapse overgrowth at the Drosophila neuromuscular junction by restricting addition of new boutons throughout larval development. dTACC localizes to the axonal MT lattice and is required to maintain tubulin levels and the integrity of higher-order MT structures in motor axon terminals. While previous reports have demonstrated the roles of MT-stabilizing proteins in promoting synapse growth, our findings suggest that in certain contexts, MT stabilization may correlate with restricted growth.
突触细胞骨架的调控对于神经元的正常发育和连接至关重要。神经元微管(MTs)的扰动与多种病理状况相关,但MTs的变化如何与突触形态发生相耦合仍不清楚。研究已经鉴定出许多促进突触生长的MT调节因子。然而,尽管突触过度生长与严重神经疾病可能存在联系,但对于限制突触生长的因素却知之甚少。在此,我们报告称,参与MT组装和稳定性的dTACC通过在整个幼虫发育过程中限制新突触小体的添加,防止果蝇神经肌肉接头处的突触过度生长。dTACC定位于轴突MT晶格,并且是维持运动轴突终末微管蛋白水平和高阶MT结构完整性所必需的。虽然先前的报告已经证明了MT稳定蛋白在促进突触生长中的作用,但我们的研究结果表明,在某些情况下,MT稳定可能与生长受限相关。