Dong Xintong, Chiu Hui, Park Yeonhee Jenny, Zou Wei, Zou Yan, Özkan Engin, Chang Chieh, Shen Kang
Department of Biology, Stanford University, Stanford, United States.
Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Elife. 2016 Mar 14;5:e11008. doi: 10.7554/eLife.11008.
Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis.
细胞外黏附分子及其神经元受体引导轴突和树突的生长与分支。生长锥被吸引至中间靶点，但到达后它们必须改变反应，以便能够离开并完成下一阶段的生长。在此，我们表明，秀丽隐杆线虫弗林蛋白酶同源物KPC-1通过将分支受体DMA-1靶向晚期内体来调节其在树突上的水平。在kpc-1突变体中，DMA-1在树突上的水平异常高，导致树突被困在存在高水平同源配体（黏附分子SAX-7/L1）的位置。DMA-1的调控异常还会导致树突自我回避缺陷。因此，对导向受体的精确调控可产生对导向信号反应的灵活性，对神经元形态发生至关重要。
