Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection.
Monotreme lactation protein is highly expressed in monotreme milk and provides antimicrobial protection.
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DOI：
10.1093/gbe/evu209
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发表时间：
2014-09-22
影响因子：
3.3
通讯作者：
Sharp JA
中科院分区：
文献类型：
--
作者：
Enjapoori AK;Grant TR;Nicol SC;Lefèvre CM;Nicholas KR;Sharp JA
单孔目动物（鸭嘴兽和针鼹）是所有现存哺乳动物最古老祖先的后代，它们以繁殖方式区别于其他哺乳动物。单目动物在短暂的妊娠期后产卵，在更短的孵化期后，晚育的幼仔在长时间的哺乳期内得到营养，乳汁由位于雌性腹部的没有乳头的乳房分泌。牛奶是发育中的幼崽直到断奶的唯一营养和免疫保护来源。通过对乳细胞和乳蛋白的转录组和质谱分析，鉴定出一种新的单链泌乳蛋白（Monotreme lact哺乳性蛋白，MLP）是乳中的主要分泌蛋白。我们发现鸭嘴兽和短喙针鼹的MLP基因具有显著的同源性，并且是单孔目动物所特有的。MLP转录本可在多种组织中表达；但在乳细胞中表达量最高，且从泌乳早期到泌乳后期均有组成性表达。对重组MLP的分析表明它是一个n -链糖基化蛋白，生物物理学研究预测MLP是一种两亲性的α-螺旋蛋白，具有抗菌蛋白的典型特征。功能分析显示，MLP对条件致病性金黄色葡萄球菌和共生粪肠球菌均有抑菌活性，但对大肠杆菌、铜绿假单胞菌、表皮葡萄球菌和肠炎沙门氏菌无抑菌作用。我们的数据表明，MLP是一种进化上古老的牛奶介导的先天免疫成分，在其他哺乳动物中不存在。我们认为，在哺乳动物没有乳头的时候，MLP在单目动物谱系中特异性进化，支持这些物种哺乳的进化，以提供细菌保护。
Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female’s abdomen. Milk is the sole source of nutrition and immune protection for the developing young until weaning. Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to monotremes. The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. We propose that MLP evolved specifically in the monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples.
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影响因子：
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