The Mechanism of Milk-Fat Secretion

乳脂分泌的机制

• 批准号: 9119264
• 负责人: Ian Mather
• 金额: $ 24.32万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9119264&HistoricalAwards=false
• 关键词: Mechanism; Milk; Fat; Secretion

This proposal addresses the mechanism, at the molecular level, underlying the secretion of milk-fat droplets from mammary epithelial cells during lactation. Fat droplets assembled in the cytoplasm are released from the surface of secretory cells coated with an outer layer of membrane. This layer gives rise to the fat- globule membrane (FGM) on the surface of fat droplets in milk. The proposed experiments will test the hypothesis that butyrophilin, the major protein of FGM, functions as a specific receptor for cytoplasmic fat droplets, and that the budding of fat droplets from the apical surface occurs through the progressive cross-linking of butyrophilin molecules to each other and to other FGM proteins via disulfide bonds. It will be determined if butyrophilin is enriched in the FGM relative to the apical plasma membrane and becomes cross-linked by disulfide bonds in the cytoplasmic domain during formation of FGM. The butyrophilin gene will be inserted into cells in culture, and into mice, to see whether butyrophilin associates with fat droplets in cells other than mammary secretory cells. Butyrophilin gene expression will be eliminated in transgenic mice to test whether milk-fat secretion is inhibited in lactating animals. %%% Exocrine secretion (cellular secretion which proceeds via exocytosis of secretory content) has become an extremely well studied aspect of cell biology, and tremendous breakthroughs in our understanding of exocytotic secretion have been and continue to take place. In contrast, apocrine secretion (secretion which proceeds by the "budding off" of apical cytoplasmic content), as typified by milk fat globule secretion, has received relatively little attention in recent years. This proposal promises to increase our understanding of the molecular mechanisms involved in milk fat secretion. In addition to contributing to fundamental knowledge of cellular processes, a better understanding of milk fat secretion will have great significance for potential biotechnological applications, such as the use of transgenic bovine milk as a source of commercially useful membrane proteins.

该提案在分子水平上解决了机制， 从乳房分泌乳脂滴的基础 哺乳期的上皮细胞。 脂肪滴聚集在 细胞质从包被的分泌细胞表面释放 有一层外层膜。 这一层产生了脂肪- 乳中脂肪滴表面的球状膜（FGM）。 的 所提出的实验将检验这样的假设， FGM的主要蛋白质，作为一种特异性受体， 细胞质脂肪滴，脂肪滴的萌芽， 顶端表面通过以下物质的逐步交联而发生 亲丁酸蛋白分子相互作用，并与其他FGM蛋白通过 二硫键 将确定亲酪蛋白是否富集 相对于顶端质膜， 通过胞质结构域中的二硫键交联， FGM的形成。 亲酪蛋白基因将被插入到 细胞培养，并进入小鼠，看看是否butyrophil 与乳腺分泌细胞以外的细胞中的脂肪滴相关 细胞 嗜酪蛋白基因表达将被消除， 转基因小鼠，以测试是否乳脂分泌受到抑制， 哺乳动物 %%% 外分泌（细胞分泌，通过 分泌内容物的胞吐作用）已经成为一种非常好的 细胞生物学的研究方面，以及我们在这方面的巨大突破， 对胞吐分泌的理解已经并将继续 发生。 相反，顶浆分泌（ 通过顶端细胞质内容物的“出芽”进行）， 以乳脂肪球分泌为代表，已收到相对 近年来很少注意。 该提案承诺， 增加我们对参与的分子机制的理解， 乳脂分泌 除了为基本的 了解细胞过程，更好地了解牛奶脂肪 分泌物将对潜在的 生物技术应用，如使用转基因牛 牛奶作为商业上有用的膜蛋白的来源。