Chondrocyte secreted CRTAC1:: A glycosylated extracellular matrix molecule of human articular cartilage
Chondrocyte secreted CRTAC1:: A glycosylated extracellular matrix molecule of human articular cartilage
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DOI：
10.1016/j.matbio.2006.09.006
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发表时间：
2007-01-01
期刊：
影响因子：
6.9
通讯作者：
Richter, Wiltrud
中科院分区：
文献类型：
--
作者：
Steck, Eric;Braeun, Jessica;Richter, Wiltrud
软骨酸性蛋白1（CRTAC 1）是一种新的人类标记物，它可以区分培养中的人软骨细胞和成骨细胞及间充质干细胞，迄今为止仅在RNA水平上进行了研究。我们在这里描述了它的基因组组织和检测一个新的脑表达（CRTAC 1-B）异构体产生的交替最后一个外显子的使用，这是高度保守的脊椎动物。在人类中，我们确定了一个外显子共享过程与相邻的尾到尾定向基因导致CRTAC 1-A。这种同种型由培养的人软骨细胞产生，定位于关节软骨的细胞外基质中，并且其分泌可以被BMP 4刺激。在CRTAC 1-A最后一个外显子中的5个假定O-糖基化基序中，根据O-糖基化抑制剂Benzyl-alpha-GalNAc对系列C-末端缺失突变体的暴露，最C-末端的基序被修饰。这两种亚型都含有四个FG-GAP重复结构域和一个RGD整合素结合基序，表明细胞-细胞或细胞-基质相互作用的潜力。总之，CRTAC 1从人类的尾对尾定向相邻基因获得了替代的最后一个外显子，导致糖基化同种型CRTAC 1-A，其代表了关节软骨的新细胞外基质分子。(c)2006年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
Cartilage acidic protein 1 (CRTAC1), a novel human marker which allowed discrimination of human chondrocytes from osteoblasts and mesenchymal stem cells in culture was so far studied only on the RNA-level. We here describe its genomic organisation and detect a new brain expressed (CRTAC1-B) isoform resulting from alternate last exon usage which is highly conserved in vertebrates. In humans, we identify an exon sharing process with the neighbouring tail-to-tail orientated gene leading to CRTAC1-A. This isoform is produced by cultured human chondrocytes, localized in the extracellular matrix of articular cartilage and its secretion can be stimulated by BMP4. Of five putative O-glycosylation motifs in the last exon of CRTAC1-A, the most C-terminal one is modified according to exposure of serial C-terminal deletion mutants to the O-glycosylation inhibitor Benzyl-alpha-GalNAc. Both isoforms contain four FG-GAP repeat domains and an RGD integrin binding motif, suggesting cell-cell or cell-matrix interaction potential. In summary, CRTAC1 acquired an alternate last exon from the tail-to-tail oriented neighbouring gene in humans resulting in the glycosylated isoform CRTAC1-A which represents a new extracellular matrix molecule of articular cartilage. (c) 2006 Elsevier B.V./International Society of Matrix Biology. All rights reserved.