cDNA cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specific proteoglycan regulated during cortical development and in glioma
cDNA cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specific proteoglycan regulated during cortical development and in glioma
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DOI：
10.1016/s0378-1119(00)00362-0
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发表时间：
2000-10-03
期刊：
影响因子：
3.5
通讯作者：
Hockfield, S
中科院分区：
文献类型：
--
作者：
Gary, SC;Zerillo, CA;Hockfield, S
BEHAB（脑富集 HyAluronan 结合）/brevican 是硫酸软骨素蛋白聚糖 (CSPG) 凝集素家族的大脑特异性成员，可能在大脑发育和人类神经胶质瘤中发挥作用。 BEHAB/brevican 已从牛、小鼠和大鼠中克隆。已报道了两种同种型：一种是分泌到细胞外基质（ECM）中的全长同种型，另一种是具有预测糖磷脂酰肌醇（GPI）锚的序列的较短同种型。在这里，我们报告了人脑中 BEHAB/brevican 亚型的表征。首先，BEHAB/brevican 映射到人类染色体 1q31。其次，我们报告了人类 BEHAB/brevican 的两种亚型的序列。推导的全长分泌型人 BEHAB/brevican 蛋白序列与牛、小鼠和大鼠同源物的同源性分别为 89.7%、83.3% 和 83.2%。第三，通过 RNase 保护分析 (RPA)，我们展示了正常人类皮质中 BEHAB/brevican 亚型的发育调节。分泌的异构体从出生到 8 岁期间高度表达，并在 20 岁时下调至正常成人皮质中维持的低水平。 GPI 同工型在整个发育过程中均以较低水平表达。第四，我们确认并扩展了我们实验室之前的研究，定量证明了人神经胶质瘤中 BEHAB/brevican mRNA 的上调。 RPA 分析表明，两种亚型在神经胶质瘤中均上调，表达量比正常水平增加约七倍。与仅调节分泌亚型的 BEHAB/brevican 的发育调节相反，两种亚型在人神经胶质瘤中平行增加。两种亚型的表达调节的不同模式表明了在发育期间和神经胶质瘤中BEHAB/brevican 的不同调节机制。 (C) 2000 Elsevier Science B.V. 保留所有权利。
BEHAB (Brain Enriched HyAluronan Binding)/brevican, a brain-specific member of the lectican family of chondroitin sulfate proteoglycans (CSPGs), may play a role in both brain development and human glioma. BEHAB/brevican has been cloned from bovine, mouse and rat. Two isoforms have been reported: a full-length isoform that is secreted into the extracellular matrix (ECM) and a shorter isoform with a sequence that predicts a glycophosphatidylinositol (GPI) anchor. Here, we report the characterization of BEHAB/brevican isoforms in human brain. First, BEHAB/brevican maps to human chromosome 1q31. Second, we report the sequence of both isoforms of human BEHAB/brevican. The deduced protein sequence of full-length, secreted human BEHAB/brevican is 89.7, 83.3 and 83.2% identical to bovine, mouse and rat homologues, respectively. Third, by RNase protection analysis (RPA) we show the developmental regulation of BEHAB/brevican isoforms in normal human cortex. The secreted isoform is highly expressed from birth through 8 years of age and is downregulated by 20 years of age to low levels that are maintained in the normal adult cortex. The GPI isoform is expressed at uniformly low levels throughout development. Fourth, we confirm and extend previous studies from our laboratory, here demonstrating the upregulation of BEHAB/brevican mRNA in human glioma quantitatively. RPA analysis shows that both isoforms are upregulated in glioma, showing an approximately sevenfold increase in expression over normal levels. In contrast to the developmental regulation of BEHAB/brevican, where only the secreted isoform is regulated, both isoforms are increased in parallel in human glioma. The distinct patterns of regulation of expression of the two isoforms suggest distinct mechanisms of regulation of BEHAB/brevican during development and in glioma. (C) 2000 Elsevier Science B.V. All rights reserved.