Feta Almir, Do Anh-Tri, Rentzsch Fabian, Technau Ulrich, Kusche-Gullberg Marion
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway.
Biochem J. 2009 May 1;419(3):585-93. doi: 10.1042/BJ20082081.
HS (heparan sulfate) proteoglycans are key regulators of vital processes in the body. HS chains with distinct sequences bind to various protein ligands, such as growth factors and morphogens, and thereby function as important regulators of protein gradient formation and signal transduction. HS is synthesized through the concerted action of many different ER (endoplasmic reticulum) and Golgi-resident enzymes. In higher organisms, many of these enzymes occur in multiple isoforms that differ in substrate specificity and spatial and temporal expression. In order to investigate how the structural complexity of HS has evolved, in the present study we focused on the starlet sea anemone (Nematostella vectensis), which belongs to the Anthozoa, which are considered to have retained many ancestral features. Members of all of the enzyme families involved in the generation and modification of HS were identified in Nematostella. Our results show that the enzymes are highly conserved throughout evolution, but the number of isoforms varies. Furthermore, the HS polymerases [Ext (exostosin) enzymes Ext1, Ext2 and Ext-like3] represent distinct subgroups, indicating that these three genes have already been present in the last common ancestor of Cnidaria and Bilateria. In situ hybridization showed up-regulation of certain enzymes in specific areas of the embryo at different developmental stages. The specific mRNA expression pattern of particular HS enzymes implies that they may play a specific role in HS modifications during larval development. Finally, biochemical analysis of Nematostella HS demonstrates that the sea anemone synthesizes a polysaccharide with a unique structure.
硫酸乙酰肝素（HS）蛋白聚糖是体内重要生理过程的关键调节因子。具有不同序列的HS链与各种蛋白质配体结合，如生长因子和形态发生素，从而作为蛋白质梯度形成和信号转导的重要调节因子发挥作用。HS是通过许多不同的内质网（ER）和高尔基体驻留酶的协同作用合成的。在高等生物中，许多这些酶以多种同工型存在，它们在底物特异性以及空间和时间表达上存在差异。为了研究HS的结构复杂性是如何进化的，在本研究中，我们聚焦于星状海葵（Nematostella vectensis），它属于珊瑚纲，被认为保留了许多祖先特征。在星状海葵中鉴定出了所有参与HS生成和修饰的酶家族成员。我们的结果表明，这些酶在整个进化过程中高度保守，但同工型的数量有所不同。此外，HS聚合酶[外切异麦芽糖基转移酶（Ext）家族的Ext1、Ext2和类Ext3]代表不同的亚组，这表明这三个基因在刺胞动物和两侧对称动物的最后一个共同祖先中就已经存在。原位杂交显示，在胚胎发育的不同阶段，特定区域的某些酶上调。特定HS酶的特定mRNA表达模式表明，它们可能在幼虫发育过程中的HS修饰中发挥特定作用。最后，对星状海葵HS的生化分析表明，海葵合成了一种具有独特结构的多糖。
