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深度覆盖小鼠红细胞蛋白质组:与人类红细胞的首次比较。

Deep coverage mouse red blood cell proteome: a first comparison with the human red blood cell.

作者信息

Pasini Erica M, Kirkegaard Morten, Salerno Doris, Mortensen Peter, Mann Matthias, Thomas Alan W

机构信息

Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands.

出版信息

Mol Cell Proteomics. 2008 Jul;7(7):1317-30. doi: 10.1074/mcp.M700458-MCP200. Epub 2008 Mar 14.

DOI:10.1074/mcp.M700458-MCP200
PMID:18344233
Abstract

Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much research has therefore focused on RBC and cardiovascular disorders of mouse and humans. RBCs also host malaria parasites. Recently we presented an in-depth proteome for the human RBC. Here we present directly comparable data for the mouse RBC as membrane-only, soluble-only, and combined membrane-bound/soluble proteomes (comprising, respectively, 247, 232, and 165 proteins). All proteins were identified, validated, and categorized in terms of subcellular localization, protein family, and function, and in comparison with the human RBC, were classified as orthologs, family-related, or unique. Splice isoforms were identified, and polypeptides migrating with anomalous apparent molecular weights were grouped into putatively ubiquitinated or partially degraded complexes. Overall there was close concordance between mouse and human proteomes, confirming the unexpected RBC complexity. Several novel findings in the human proteome have been confirmed here. This comparison sheds light on several open issues in RBC biology and provides a departure point for more comprehensive understanding of RBC function.

摘要

小鼠与人类有着密切的遗传/生理关系,繁殖迅速,且可进行基因改造,这使其成为生物医学研究中使用最为广泛的哺乳动物。由于红细胞(RBC)是脊椎动物中唯一的气体转运体,红细胞疾病往往较为严重;因此,许多研究都聚焦于小鼠和人类的红细胞及心血管疾病。红细胞也是疟原虫的宿主。最近我们公布了人类红细胞的深度蛋白质组。在此,我们展示了与小鼠红细胞直接可比的数据,包括仅膜蛋白、仅可溶性蛋白以及结合膜/可溶性蛋白组合(分别包含247、232和165种蛋白质)。所有蛋白质均依据亚细胞定位、蛋白家族和功能进行了鉴定、验证和分类,并且与人类红细胞相比,被归类为直系同源物、家族相关蛋白或独特蛋白。鉴定出了剪接异构体,迁移时具有异常表观分子量的多肽被归类为假定泛素化或部分降解的复合物。总体而言,小鼠和人类蛋白质组之间存在密切的一致性,证实了红细胞出人意料的复杂性。人类蛋白质组中的一些新发现在此得到了证实。这种比较揭示了红细胞生物学中的几个未解决问题,并为更全面地理解红细胞功能提供了一个出发点。

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