A network of HSPG core proteins and HS modifying enzymes regulates netrin-dependent guidance of D-type motor neurons in Caenorhabditis elegans.
A network of HSPG core proteins and HS modifying enzymes regulates netrin-dependent guidance of D-type motor neurons in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0074908
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hengartner MO
中科院分区：
文献类型：
--
作者：
Gysi S;Rhiner C;Flibotte S;Moerman DG;Hengartner MO
硫酸乙酰肝素蛋白聚糖 (HSPG) 是具有长共价连接的硫酸乙酰肝素 (HS) 类型糖侧链的蛋白质。根据细胞环境，HS 链带有多种结构修饰，例如硫酸盐残基或差向异构糖，使它们能够与多种分子结合。人们发现 HSPG 在动物发育中发挥着极其不同的作用，并且与某些轴突引导分子相互作用。在这项研究中，我们描述了秀丽隐杆线虫 HSPG 核心蛋白 Syndecan (SDN-1) 和 Glypican (LON-2) 以及 HS 修饰酶在 D 型运动轴突背侧引导中的作用，该过程主要由保守的轴突引导分子 UNC-6/Netrin 控制。我们的遗传分析确定了与该轴突引导事件相关的特定 HS 代码。利用两种敏化遗传背景，我们分离出了影响 D 型运动轴突引导的新成分（与 HSPG 相关），以及几个先前表征的轴突引导基因的新等位基因。有趣的是，zfp-1 或 lin-35 突变引起的背侧轴突引导缺陷取决于用于可视化 D 型运动神经元的转基因 oxIs12。 oxIs12 是一种大型多拷贝转基因，可将 X 染色体扩大约 20%。在寻找具有可比表型的基因时，我们发现已知剂量补偿基因 dpy-21 中的突变显示出与 zfp-1 或 lin-35 突变体类似的轴突引导缺陷。因此，X 上的基因去抑制（许多与 HS 依赖性轴突引导相关的基因位于此处）也可能影响 D 型运动神经元的轴突引导。
Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons.
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影响因子：
64.5
作者：
Belenkaya, TY;Han, C;Lin, XH
通讯作者：
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影响因子：
4.5
作者：
Cui, Mingxue;Kim, E. Bridget;Han, Min
通讯作者：
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影响因子：
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作者：
Chinnam, Meenalakshmi;Goodrich, David W.
通讯作者：
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影响因子：
3.3
作者：
Flibotte, Stephane;Edgley, Mark L.;Moerman, Donald G.
通讯作者：
Moerman, Donald G.
DOI：
10.1073/pnas.0810589105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Grishok, Alla;Hoersch, Sebastian;Sharp, Phillip A.
通讯作者：
Sharp, Phillip A.