Kamiyama Daichi, McGorty Ryan, Kamiyama Rie, Kim Michael D, Chiba Akira, Huang Bo
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Dev Cell. 2015 Oct 12;35(1):93-106. doi: 10.1016/j.devcel.2015.09.007.
Precise positioning of dendritic branches is a critical step in the establishment of neuronal circuitry. However, there is limited knowledge on how environmental cues translate into dendrite initiation or branching at a specific position. Here, through a combination of mutation, RNAi, and imaging experiments, we found that a Dscam-Dock-Pak1 hierarchical interaction defines the stereotypical dendrite growth site in the Drosophila aCC motoneuron. This interaction localizes the Cdc42 effector Pak1 to the plasma membrane at the dendrite initiation site before the activation of Cdc42. Ectopic expression of membrane-anchored Pak1 overrides this spatial specification of dendritogenesis, confirming its function in guiding Cdc42 signaling. We further discovered that Dscam1 localization in aCC occurs through an inter-neuronal contact that involves Dscam1 in the partner MP1 neuron. These findings elucidate a mechanism by which Dscam1 controls neuronal morphogenesis through spatial regulation of Cdc42 signaling and, subsequently, cytoskeletal remodeling.
树突分支的精确定位是神经元回路建立过程中的关键步骤。然而，关于环境线索如何转化为特定位置的树突起始或分支，我们所知有限。在这里，通过突变、RNA干扰和成像实验的结合，我们发现Dscam-Dock-Pak1分级相互作用定义了果蝇aCC运动神经元中 stereotypical 树突生长位点。这种相互作用在Cdc42激活之前将Cdc42效应器Pak1定位到树突起始位点的质膜上。膜锚定Pak1的异位表达覆盖了树突发生的这种空间特异性，证实了其在引导Cdc42信号传导中的作用。我们进一步发现，aCC中Dscam1的定位是通过涉及伙伴MP1神经元中Dscam1的神经元间接触实现的。这些发现阐明了一种机制，即Dscam1通过对Cdc42信号传导的空间调节以及随后的细胞骨架重塑来控制神经元形态发生。
