Lamanna William C, Kalus Ina, Padva Michael, Baldwin Rebecca J, Merry Catherine L R, Dierks Thomas
Department of Chemistry, Biochemistry I, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany.
J Biotechnol. 2007 Apr 30;129(2):290-307. doi: 10.1016/j.jbiotec.2007.01.022. Epub 2007 Feb 8.
Heparan sulfate (HS) is a cell surface carbohydrate polymer modified with sulfate moieties whose highly ordered composition is central to directing specific cell signaling events. The ability of the cell to generate these information rich glycans with such specificity has opened up a new field of "heparanomics" which seeks to understand the systems involved in generating these cell type and developmental stage specific HS sulfation patterns. Unlike other instances where biological information is encrypted as linear sequences in molecules such as DNA, HS sulfation patterns are generated through a non-template driven process. Thus, deciphering the sulfation code and the dynamic nature of its generation has posed a new challenge to system biologists. The recent discovery of two sulfatases, Sulf1 and Sulf2, with the unique ability to edit sulfation patterns at the cell surface, has opened up a new dimension as to how we understand the regulation of HS sulfation patterning and pattern-dependent cell signaling events. This review will focus on the functional relationship between HS sulfation patterning and biological processes. Special attention will be given to Sulf1 and Sulf2 and how these key editing enzymes might act in concert with the HS biosynthetic enzymes to generate and regulate specific HS sulfation patterns in vivo. We will further explore the use of knock out mice as biological models for understanding the dynamic systems involved in generating HS sulfation patterns and their biological relevance. A brief overview of new technologies and innovations summarizes advances in the systems biology field for understanding non-template molecular networks and their influence on the "heparanome".
硫酸乙酰肝素（HS）是一种经硫酸基团修饰的细胞表面碳水化合物聚合物，其高度有序的组成对于指导特定的细胞信号传导事件至关重要。细胞以如此高的特异性生成这些富含信息的聚糖的能力开辟了一个新的“硫酸乙酰肝素组学”领域，该领域旨在了解参与生成这些细胞类型和发育阶段特异性HS硫酸化模式的系统。与生物信息以线性序列形式加密在DNA等分子中的其他情况不同，HS硫酸化模式是通过非模板驱动的过程生成的。因此，破译硫酸化密码及其生成的动态性质给系统生物学家带来了新的挑战。最近发现了两种硫酸酯酶Sulf1和Sulf2，它们具有在细胞表面编辑硫酸化模式的独特能力，这为我们理解HS硫酸化模式的调控以及模式依赖性细胞信号传导事件开辟了一个新的维度。本综述将重点关注HS硫酸化模式与生物过程之间的功能关系。将特别关注Sulf1和Sulf2，以及这些关键的编辑酶如何与HS生物合成酶协同作用，在体内生成和调节特定的HS硫酸化模式。我们将进一步探讨使用基因敲除小鼠作为生物学模型，以了解参与生成HS硫酸化模式的动态系统及其生物学相关性。对新技术和创新的简要概述总结了系统生物学领域在理解非模板分子网络及其对“硫酸乙酰肝素组”的影响方面取得的进展。
