Proteolytic Control of Neuronal Differentiation

神经元分化的蛋白水解控制

• 批准号: 6655695
• 负责人: James I Kim
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6655695
• 关键词: cell differentiation; gene deletion mutation; gene expression; gene targeting; genetically modified animals; in situ hybridization; laboratory mouse; molecular site; neurogenesis; northern blottings; phenotype; pluripotent stem cells; postdoctoral investigator; protease inhibitor; proteolysis

We have discovered a secreted, soluble protein that is able to inhibit primary neurogenesis in Xenopus embryos. This 394 amino acid protein contains three serine proteinase inhibitor domains of the Kunitz class. This novel protein has been named Trinein and was isolated during a differential screen for maternally-encoded mRNAs present in the Xenopus laevis egg. Strikingly, microinjection of Trinein mRNA into Xenopus embryos seems to have little effect on mesodermal (marked by Xbra, sonic hedgehog, chordin) and neural plate (marked by Sox-2) cell differentiation; however, differentiation of definitive mature neurons (positive for neurotubulin and neurogenin) is blocked in the neural plate (unpublished data). This proposal builds upon these functional data of Trinein to understand its function in mammalian neurogenesis.

我们已经发现了一种分泌的可溶性蛋白，能够抑制爪蟾胚胎的初级神经发生。这种394个氨基酸的蛋白质含有三个Kunitz类丝氨酸蛋白酶抑制剂结构域。这种新的蛋白质被命名为Trinein，并在非洲爪蟾卵中存在的母亲编码的mRNA的差异筛选过程中分离出来。引人注目的是，将Trinein mRNA显微注射到非洲爪蟾胚胎中似乎对中胚层（由Xbra、音刺猬蛋白、脊索蛋白标记）和神经板（由Sox-2标记）细胞分化几乎没有影响;然而，神经板中永久成熟神经元（神经微管蛋白和神经原蛋白阳性）的分化被阻断（未发表的数据）。该建议基于Trinein的这些功能数据来理解其在哺乳动物神经发生中的功能。