Laboratory for Genetic Control of Neuronal Architecture, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan.
Graduate School of Science and Engineering, Saitama University, Sakura-ku, Saitama, Japan.
Nat Neurosci. 2015 Oct;18(10):1437-45. doi: 10.1038/nn.4099. Epub 2015 Aug 31.
Neuronal dendrite branching is fundamental for building nervous systems. Branch formation is genetically encoded by transcriptional programs to create dendrite arbor morphological diversity for complex neuronal functions. In Drosophila sensory neurons, the transcription factor Abrupt represses branching via an unknown effector pathway. Targeted screening for branching-control effectors identified Centrosomin, the primary centrosome-associated protein for mitotic spindle maturation. Centrosomin repressed dendrite branch formation and was used by Abrupt to simplify arbor branching. Live imaging revealed that Centrosomin localized to the Golgi cis face and that it recruited microtubule nucleation to Golgi outposts for net retrograde microtubule polymerization away from nascent dendrite branches. Removal of Centrosomin enabled the engagement of wee Augmin activity to promote anterograde microtubule growth into the nascent branches, leading to increased branching. The findings reveal that polarized targeting of Centrosomin to Golgi outposts during elaboration of the dendrite arbor creates a local system for guiding microtubule polymerization.
神经元树突分支是构建神经系统的基础。分支形成是由转录程序遗传编码的,为复杂的神经元功能创造树突分支形态多样性。在果蝇感觉神经元中,转录因子 Abrupt 通过未知的效应途径抑制分支形成。靶向筛选分支控制效应物鉴定了中心体蛋白 Centrosomin,它是有丝分裂纺锤体成熟的主要中心体相关蛋白。Centrosomin 抑制树突分支形成,并被 Abrupt 用于简化树突分支。实时成像显示 Centrosomin 定位于高尔基 cis 面,它招募微管核形成到高尔基突出部,用于从新生树突分支净逆行微管聚合。去除 Centrosomin 使 wee Augmin 活性能够参与,促进微管正向生长进入新生分支,从而增加分支。研究结果表明,在树突分支的精细加工过程中,Centrosomin 向高尔基突出部的极化靶向为微管聚合提供了一个局部导向系统。