Glycosylation Specific for Adhesion Molecules in Epidermis and Its Receptor Revealed by Glycoform-focused Reverse Genomics
Glycosylation Specific for Adhesion Molecules in Epidermis and Its Receptor Revealed by Glycoform-focused Reverse Genomics
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DOI：
10.1074/mcp.m800145-mcp200
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发表时间：
2009-02-01
影响因子：
7
通讯作者：
Nishimura, Shin-Ichiro
中科院分区：
文献类型：
--
作者：
Uematsu, Rie;Shinohara, Yasuro;Nishimura, Shin-Ichiro
蛋白质的糖基化极大地影响其结构和功能，但传统的基因组学和转录组学无法精确捕获组织或物种特异性糖基化模式。我们在这里描述了一种新的方法来连接不同的“组学”数据的基础上详尽的定量糖组学的小鼠真皮和表皮。我们首先研究了真皮和表皮的N-糖最近建立的糖印迹技术。我们发现Gal α 1 - 3Gal表位仅在表皮组织中表达，并以糖基化位点特异性方式优先附着于粘附分子。澄清的糖组学和蛋白质组学信息与公开可用的微阵列数据集相结合，使我们能够将半乳糖凝集素-3鉴定为Gal α 1 - 3Gal表位的受体。这些发现提供了对α 3GalT-1缺陷小鼠和表达内-β-半乳糖苷酶C的转基因小鼠中所见的基因型和表型之间因果关系的机制性见解。因为人类在其组织上不具有Gal α 1 - 3Gal结构，所以我们进一步检查了人类真皮和表皮N-糖组。比较糖组学揭示GalNAc β 1 - 4GlcNAc（N，N'-二乙酰基乳糖二胺）表位而不是Gal α 1 - 3Gal表位在人表皮中高度表达。Molecular & Cellular Proteomics 8：232 - 244，2009.
Glycosylation of proteins greatly affects their structure and function, but traditional genomics and transcriptomics are not able to precisely capture tissue- or species-specific glycosylation patterns. We describe here a novel approach to link different "omics" data based on exhaustive quantitative glycomics of murine dermis and epidermis. We first examined the dermal and epidermal N-glycome of mouse by a recently established glycoblotting technique. We found that the Gal alpha 1-3Gal epitope was solely expressed in epidermis tissue and was preferentially attached to adhesion molecules in a glycosylation site-specific manner. Clarified glycomic and protemic information combined with publicly available microarray data sets allowed us to identify galectin-3 as a receptor of Gal alpha 1-3Gal epitope. These findings provide mechanistic insight into the causal connection between the genotype and the phenotype seen in alpha 3GalT-1-deficient mice and transgenic mice expressing endo-beta-galactosidase C. Because humans do not possess the Gal alpha 1-3Gal structure on their tissues, we further examined the human dermal and epidermal N-glycome. Comparative glycomics revealed that the GalNAc beta 1-4GlcNAc ( N, N'-diacetyllactosediamine) epitope, instead of the Gal alpha 1-3Gal epitope, was highly expressed in human epidermis. Molecular & Cellular Proteomics 8:232-244, 2009.