Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604.
Department of Biological Sciences, National University of Singapore, Singapore 117543.
Development. 2020 Oct 9;147(19):dev191155. doi: 10.1242/dev.191155.
Neuronal pruning is essential for proper wiring of the nervous systems in invertebrates and vertebrates. ddaC sensory neurons selectively prune their larval dendrites to sculpt the nervous system during early metamorphosis. However, the molecular mechanisms underlying ddaC dendrite pruning remain elusive. Here, we identify an important and cell-autonomous role of the membrane protein Raw in dendrite pruning of ddaC neurons. Raw appears to regulate dendrite pruning via a novel mechanism, which is independent of JNK signaling. Importantly, we show that Raw promotes endocytosis and downregulation of the conserved L1-type cell-adhesion molecule Neuroglian (Nrg) prior to dendrite pruning. Moreover, Raw is required to modulate the secretory pathway by regulating the integrity of secretory organelles and efficient protein secretion. Mechanistically, Raw facilitates Nrg downregulation and dendrite pruning in part through regulation of the secretory pathway. Thus, this study reveals a JNK-independent role of Raw in regulating the secretory pathway and thereby promoting dendrite pruning.
神经元修剪对于无脊椎动物和脊椎动物神经系统的正确布线至关重要。ddaC 感觉神经元在早期变态期间选择性地修剪其幼虫树突，以塑造神经系统。然而，ddaC 树突修剪的分子机制仍难以捉摸。在这里，我们确定了膜蛋白 Raw 在 ddaC 神经元树突修剪中的重要和细胞自主作用。Raw 似乎通过一种新颖的机制来调节树突修剪，该机制独立于 JNK 信号。重要的是，我们表明，Raw 通过促进保守的 L1 型细胞粘附分子 Neuroglian (Nrg) 的内吞作用和下调来促进树突修剪。此外，Raw 通过调节分泌细胞器的完整性和有效的蛋白质分泌来调节分泌途径。从机制上讲，Raw 通过调节分泌途径促进 Nrg 下调和树突修剪。因此，这项研究揭示了 Raw 在调节分泌途径并促进树突修剪方面的 JNK 独立作用。
