Sasisekharan Ram, Raman Rahul, Prabhakar Vikas
Biological Engineering Division, Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Annu Rev Biomed Eng. 2006;8:181-231. doi: 10.1146/annurev.bioeng.8.061505.095745.
Extracellular modulation of phenotype is an emerging paradigm in this current postgenomics age of molecular and cell biology. Glycosaminoglycans (GAGs) are primary components of the cell surface and the cell-extracellular matrix (ECM) interface. Advances in the technology to analyze GAGs and in whole-organism genetics have led to a dramatic increase in the known important biological role of these complex polysaccharides. Owing to their ubiquitous distribution at the cell-ECM interface, GAGs interact with numerous proteins and modulate their activity, thus impinging on fundamental biological processes such as cell growth and development. Many recent reviews have captured important aspects of GAG structure and biosynthesis, GAG-protein interactions, and GAG biology. GAG research is currently at a stage where there is a need for an integrated systems or glycomics approach, which involves an integration of all of the above concepts to define their structure-function relationships. Focusing on heparin/heparan (HSGAGs) and chondroitin/dermatan sulfate (CSGAGs), this review highlights the important aspects of GAGs and summarizes these aspects in the context of taking a glycomics approach that integrates the different technologies to define structure-function relationships of GAGs.
在当前这个分子与细胞生物学的后基因组时代,表型的细胞外调节是一个新兴的范例。糖胺聚糖(GAGs)是细胞表面以及细胞 - 细胞外基质(ECM)界面的主要成分。分析GAGs的技术以及全生物体遗传学的进展,使得这些复杂多糖已知的重要生物学作用显著增加。由于它们在细胞 - ECM界面广泛分布,GAGs与众多蛋白质相互作用并调节其活性,从而影响细胞生长和发育等基本生物学过程。最近的许多综述涵盖了GAG结构与生物合成、GAG - 蛋白质相互作用以及GAG生物学的重要方面。目前GAG研究正处于需要一种综合系统或糖组学方法的阶段,该方法涉及整合上述所有概念以定义它们的结构 - 功能关系。本文聚焦于肝素/硫酸乙酰肝素(HSGAGs)和硫酸软骨素/硫酸皮肤素(CSGAGs),强调了GAGs的重要方面,并在采用整合不同技术以定义GAGs结构 - 功能关系的糖组学方法的背景下总结了这些方面。