Conservation of anatomically restricted glycosaminoglycan structures in divergent nematode species
Conservation of anatomically restricted glycosaminoglycan structures in divergent nematode species
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DOI：
10.1093/glycob/cww037
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发表时间：
2016-08-01
期刊：
影响因子：
4.3
通讯作者：
Bulow, Hannes E.
中科院分区：
文献类型：
--
作者：
Attreed, Matthew;Saied-Santiago, Kristian;Bulow, Hannes E.
硫酸乙酰肝素 (HS) 是细胞外基质的糖胺聚糖，其特点是由于硫酸化、差向异构化和乙酰化而具有复杂的修饰模式。不同的 HS 修饰模式已被证明可以调节一般发育过程中的蛋白质-蛋白质相互作用，特别是神经系统的发育过程中。这导致了硫酸乙酰肝素密码假说，该假说假设经过特殊修饰的 HS 表位以组织和细胞特异性的方式分布，以协调神经回路的形成。 HS 代码是否存在于体内、HS 代码的解剖分布的特异性或进化保守性仍然未知。在这里，我们使用 33 种不同 HS 特异性单链可变片段抗体的转基因表达，对线虫秀丽隐杆线虫中的 HS 修饰模式进行了系统比较。我们发现一些 HS 修饰模式广泛分布在神经系统中。相比之下，其他 HS 修饰模式在非神经元和神经元细胞中都表现出高度的细胞特异性。某些模式的定位可能受到单个神经突或两个神经元之间突触连接的限制。这种特定 HS 模式的受限解剖定位在不同的线虫物种 Caenorhabditis briggsae 中可以在 80-1 亿年的进化过程中得到保守，这表明与蛋白质相似的糖胺聚糖结构在结构上和可能的功能上得到了保守。这些发现表明，HS 代码在神经系统中具有亚细胞定位、独特的聚糖特性。
Heparan sulfates ( HS) are glycosaminoglycans of the extracellular matrices and characterized by complex modification patterns owing to sulfations, epimerization, and acetylation. Distinct HS modification patterns have been shown to modulate protein-protein interactions during development in general and of the nervous system in particular. This has led to the heparan sulfate code hypothesis, which posits that specifically modified HS epitopes are distributed in a tissue and cell-specific fashion to orchestrate neural circuit formation. Whether an HS code exists in vivo, how specific or how evolutionarily conserved the anatomical distribution of an HS code may be has remained unknown. Here we conduct a systematic comparison of HS modification patterns in the nematode Caenorhabditis elegans using transgenic expression of 33 different HS-specific single chain variable fragment antibodies. We find that some HS modification patterns are widely distributed in the nervous system. In contrast, other HS modification patterns appear highly cell-specific in both non-neuronal and neuronal cells. Some patterns can be as restricted in their localization as to single neurites or synaptic connections between two neurons. This restricted anatomical localization of specific HS patterns can be evolutionarily conserved over a span of 80-100 million years in the divergent nematode species Caenorhabditis briggsae suggesting structural and, possibly functional conservation of glycosaminoglycan structures similar to proteins. These findings suggest a HS code with subcellularly localized, unique glycan identities in the nervous system.