The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration.
The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration.
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DOI：
10.1016/j.ydbio.2015.01.007
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发表时间：
2015-03
影响因子：
2.7
通讯作者：
Xiangming Wang;Jianhong Liu;Zhiwen Zhu;Guangshuo Ou
中科院分区：
文献类型：
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作者：
Xiangming Wang;Jianhong Liu;Zhiwen Zhu;Guangshuo Ou
定向细胞迁移是神经发育的基础，细胞外因子是这一过程的关键。硫酸乙酰肝素蛋白聚糖（HSPG）携带长链的差异修饰的糖残基有助于细胞外基质，然而，HSPG在引导细胞迁移的功能仍然难以捉摸。在这里，我们使用了来自百万突变项目的秀丽隐杆线虫突变体库，并分离出硫酸乙酰肝素修饰酶葡萄糖醛酸C5-差向异构酶HSE-5的突变等位基因。这种酶的功能丧失导致有缺陷的Q成神经细胞迁移。我们发现thathse-5以细胞非自主的方式控制Q细胞的迁移。通过对hse-5突变动物进行活细胞成像，我们发现hse-5控制着Q神经母细胞迁移过程中的初始极化。此外，我们的遗传上位性分析表明lon-2可能作用于hse-5的下游。最后，通过表达人和小鼠hse-5同源物来拯救hse-5突变表型，表明该基因在神经发育中具有保守的功能。总之，我们的研究结果表明，HSE-5在细胞外基质中的适当HSPG修饰对于迁移过程中的成神经细胞极性是必不可少的。
Directional cell migration is fundamental for neural development, and extracellular factors are pivotal for this process. Heparan sulfate proteoglycans (HSPGs) that carry long chains of differentially modified sugar residues contribute to extracellular matrix; however, the functions of HSPG in guiding cell migration remain elusive. Here, we used theCaenorhabditis elegansmutant pool from the Million Mutation Project and isolated a mutant allele of the heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5. Loss-of-function of this enzyme resulted in defective Q neuroblast migration. We showed thathse-5controlled Q cell migration in a cell non-autonomous manner. By performing live cell imaging inhse-5mutant animals, we found thathse-5controlled initial polarization during Q neuroblast migration. Furthermore, our genetic epistasis analysis demonstrated thatlon-2might act downstream ofhse-5. Finally, rescue of thehse-5mutant phenotype by expression of human and mousehse-5homologs suggested a conserved function for this gene in neural development. Taken together, our results indicated that proper HSPG modification in the extracellular matrix by HSE-5 is essential for neuroblast polarity during migration.