Division of Biological Science, Nagoya University Graduate School of Science, Nagoya, Japan.
Genes Cells. 2020 Jun;25(6):391-401. doi: 10.1111/gtc.12765. Epub 2020 Apr 7.
Vesicular transport serves as an important mechanism for cell shape regulation during development. Although the semaphorin signaling molecule, a well-known regulator of axon guidance, induces endocytosis in the growth cone and the axonal transport of vertebrate neurons, the underlying molecular mechanisms remain largely unclear. Here, we show that the Caenorhabditis elegans SNT-1/synaptotagmin-UNC-41/stonin2 system, whose role in synaptic vesicle recycling in neurons has been studied extensively, is involved in semaphorin-regulated vesicular transport in larval epidermal cells. Mutations in the snt-1/unc-41 genes strongly suppressed the cell shape defects of semaphorin mutants. The null mutation in the semaphorin receptor gene, plx-1, altered the expression and localization pattern of endocytic and exocytic markers in the epidermal cells while repressing the transport of SNT-1-containing vesicles toward late endosome/lysosome pathways. Our findings suggest that the nematode semaphorins regulate the vesicular transport in epidermal cells in a manner distinct from that of vertebrate semaphorins in neurons.
囊泡运输是细胞在发育过程中调节形状的重要机制。尽管 semaphorin 信号分子是轴突导向的著名调节剂，可诱导生长锥内的内吞作用和脊椎动物神经元的轴突运输，但其潜在的分子机制在很大程度上仍不清楚。在这里，我们表明，Caenorhabditis elegans 的 SNT-1/synaptotagmin-UNC-41/stonin2 系统，其在神经元中突触囊泡再循环中的作用已被广泛研究，参与了幼虫表皮细胞中 semaphorin 调节的囊泡运输。snt-1/unc-41 基因突变强烈抑制了 semaphorin 突变体的细胞形状缺陷。 semaphorin 受体基因 plx-1 的缺失突变改变了表皮细胞中内吞和外排标记物的表达和定位模式，同时抑制了含有 SNT-1 的囊泡向晚期内体/溶酶体途径的运输。我们的研究结果表明，线虫 semaphorin 以不同于神经元中脊椎动物 semaphorin 的方式调节表皮细胞中的囊泡运输。
