Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide.
Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide.
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或者，剪接的II型Procollagen mRNA定义了椎骨发育过程中的不同细胞种群：氨基甲基肽的差异表达。
DOI：
10.1083/jcb.114.6.1307
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发表时间：
1991-09
期刊：
影响因子：
--
通讯作者：
Goldring MB
中科院分区：
文献类型：
--
作者：
Sandell LJ;Morris N;Robbins JR;Goldring MB
II型胶原蛋白是软骨的主要成分，为组织提供结构完整性。II型前胶原可以通过初级基因转录物的差异剪接以两种形式表达。这两种mRNA包括（IIA型）或不包括（IIB型）编码氨基（NH 2）-前肽的主要部分的外显子（外显子2）（Ryan，M. C.的方法，和L. J·桑德尔1990. J.Biol.Chem.265：10334-10339）。检测两种前胶原的表达，以确定两种II型前胶原mRNA的潜在功能意义。首先，为了确定这两种mRNA是否有功能，我们证明了这两种mRNA都可以被翻译，并且蛋白质分泌到细胞外环境中。这两种蛋白被鉴定为II型前胶原。其次，为了检验II型前胶原的差异表达可能是不同细胞群体的标志物这一假设，通过与跨越外显子连接的寡核苷酸原位杂交将特定前胶原mRNA定位于组织中。选择胚胎脊柱作为经历快速软骨形成的组织来源，允许检查与软骨相关的各种细胞类型。在这个问题上，每个前胶原mRNA在软骨形成过程中具有不同的组织分布，IIB型在软骨细胞中表达，IIA型在前软骨细胞中软骨周围的细胞中表达。表达两种胶原类型的细胞的形态是不同的：表达IIA型的细胞在外观上是窄的、细长的和“成纤维细胞”的，而表达IIB型的细胞是大的和圆的。IIB型的表达似乎与软骨细胞外基质的大量合成和积累相关。IIB型的表达在空间上与软骨蛋白聚糖、聚集蛋白聚糖的高水平表达相关，从而确立了IIB型前胶原和聚集蛋白聚糖作为软骨细胞表型的标志物。II型胶原的转录物，主要是IIA型，也在胚胎脊神经节中表达。虽然以前在非软骨组织中检测到少量的II型胶原蛋白，但在胚胎神经组织中检测到相对高丰度的这种新形式的胶原蛋白是独特的。两者合计，这些发现意味着IIA型和IIB型前胶原之间的潜在功能差异，并表明从前mRNA中去除外显子2，从而从胶原分子中去除NH 2-前肽，可能是软骨形成中的重要步骤。此外，II型前胶原，特别是IIA型，可能在非软骨组织中起作用，特别是在发育过程中。
Type II collagen is a major component of cartilage providing structural integrity to the tissue. Type II procollagen can be expressed in two forms by differential splicing of the primary gene transcript. The two mRNAs either include (type IIA) or exclude (type IIB) an exon (exon 2) encoding the major portion of the amino (NH2)-propeptide (Ryan, M. C., and L. J. Sandell. 1990. J. Biol. Chem. 265:10334-10339). The expression of the two procollagens was examined in order to establish a potential functional significance for the two type II procollagen mRNAs. First, to establish whether the two mRNAs are functional, we showed that both mRNAs can be translated and the proteins secreted into the extracellular environment. Both proteins were identified as type II procollagens. Secondly, to test the hypothesis that differential expression of type II procollagens may be a marker for a distinct population of cells, specific procollagen mRNAs were localized in tissue by in situ hybridization to oligonucleotides spanning the exon junctions. Embryonic vertebral column was chosen as a source of tissue undergoing rapid chondrogenesis, allowing the examination of a variety of cell types related to cartilage. In this issue, each procollagen mRNA had a distinct tissue distribution during chondrogenesis with type IIB expressed in chondrocytes and type IIA expressed in cells surrounding cartilage in prechondrocytes. The morphology of the cells expressing the two collagen types was distinct: the cells expressing type IIA are narrow, elongated, and "fibroblastic" in appearance while the cells expressing type IIB are large and round. The expression of type IIB appears to be correlated with abundant synthesis and accumulation of cartilagenous extracellular matrix. The expression of type IIB is spatially correlated with the high level expression of the cartilage proteoglycan, aggrecan, establishing type IIB procollagen and aggrecan as markers for the chondrocyte phenotype. Transcripts of type II collagen, primarily type IIA, are also expressed in embryonic spinal ganglion. While small amounts of type II collagen have been previously detected in noncartilagenous tissues, the detection of this new form of the collagen in relatively high abundance in embryonic nerve tissue is unique. Taken together, these findings imply a potential functional difference between type IIA and type IIB procollagens and indicate that the removal of exon 2 from the pre-mRNA, and consequently the NH2- propeptide from the collagen molecule, may be an important step in chondrogenesis. In addition, type II procollagen, specifically type IIA, may function in noncartilage tissues, particularly during development.