Brorin, a novel secreted bone morphogenetic protein antagonist, promotes neurogenesis in mouse neural precursor cells
Brorin, a novel secreted bone morphogenetic protein antagonist, promotes neurogenesis in mouse neural precursor cells
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DOI：
10.1074/jbc.m701570200
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发表时间：
2007-05-25
影响因子：
4.8
通讯作者：
Itoh, Nobuyuki
中科院分区：
文献类型：
--
作者：
Koike, Naomi;Kassai, Yoshiaki;Itoh, Nobuyuki
我们在小鼠和人类中鉴定出了编码一种新型分泌蛋白的基因，并将其命名为 Brorin。小鼠 Brorin 由 324 个氨基酸组成，其氨基末端有一个推定的分泌信号序列，其核心区域有两个富含半胱氨酸的结构域。 Brorin 结构域中 10 个半胱氨酸残基的位置与 Chordin 家族成员富含半胱氨酸的结构域中的位置相似。然而，布罗林的氨基酸序列与脊索蛋白家族的任何其他成员的氨基酸序列并不显着相似，这表明布罗林是该家族的独特成员。培养细胞中产生的小鼠布洛林蛋白被有效地分泌到培养基中。该蛋白抑制小鼠前成骨细胞 MC3T3-E1 细胞中骨形态发生蛋白 2 (BMP2) 和 BMP6 的活性。小鼠 Brorin 主要在胚胎神经组织中表达，也主要在成年大脑中表达。在大脑中，在神经元中检测到该表达，但在神经胶质细胞中未检测到。 Brorin 的神经组织特异性表达谱与 Chordin 家族的任何其他成员都截然不同。溴蛋白促进小鼠神经前体细胞中的神经发生，但不促进星形细胞发生。目前的研究结果表明 Brorin 是一种新型分泌型 BMP 拮抗剂，可能在神经发育和功能中发挥作用。
We identified a gene encoding a novel secreted protein in mice and humans and named it Brorin. Mouse Brorin consists of 324 amino acids with a putative secreted signal sequence at its amino terminus and two cysteine-rich domains in its core region. Positions of 10 cysteine residues in the domains of Brorin are similar to those in the cysteine-rich domains of members of the Chordin family. However, the amino acid sequence of Brorin is not significantly similar to that of any other member of the Chordin family, indicating that Brorin is a unique member of the family. Mouse Brorin protein produced in cultured cells was efficiently secreted into the culture medium. The protein inhibited the activity of bone morphogenetic protein 2 (BMP2) and BMP6 in mouse preosteoblastic MC3T3-E1 cells. Mouse Brorin was predominantly expressed in neural tissues in embryos and also predominantly expressed in the adult brain. In the brain, the expression was detected in neurons, but not glial cells. The neural tissue-specific expression profile of Brorin is quite distinct from that of any other member of the Chordin family. Brorin protein promoted neurogenesis, but not astro-genesis, in mouse neural precursor cells. The present findings indicate that Brorin is a novel secreted BMP antagonist that potentially plays roles in neural development and functions.