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【Nature】Nature：肾脏起源于昆虫？
现在Weavers等人报告，昆虫的一种被称为“肾原细胞”的过滤细胞与“足细胞”有惊人的相似之处。肾脏裂孔隔膜主要成分的果蝇直系同源物形成一种由相互作用的蛋白构成的复合物，与脊椎动物中的相似。“肾原细胞”隔膜在肾病蛋白或neph1直系同源基因的果蝇突变体中完全丢失，与人类肾病—— “先天性肾病综合征”(NPHS1)的表现型相似。这一发现将昆虫“肾原细胞”确定为研究肾脏“足细胞”生物学及与“足细胞”相关疾病的一个模型。
Nature 457, 322-326 (15 January 2009) | doi:10.1038/nature07526
The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm
Helen Weavers1,6, Silvia Prieto-Sánchez2,6, Ferdinand Grawe3, Amparo Garcia-López4, Ruben Artero4, Michaela Wilsch-Br?uninger5, Mar Ruiz-Gómez2, Helen Skaer1 & Barry Denholm1
1 Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK
2 Centro de Biología Molecular Severo Ochoa, CSIC, UAM, Cantoblanco, 28049 Madrid, Spain
3 Institut für Genetik, Heinrich-Heine-Universit?t, Düsseldorf D-40225, Germany
4 Department of Genetics, University of Valencia, Burjasot, Valencia 46100, Spain
5 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden D-01307, Germany
The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation1, 'nephron-like' features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors2. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity to the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialized filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly (Drosophila melanogaster) orthologues of the major constituents of the slit diaphragm, including nephrin, NEPH1 (also known as KIRREL), CD2AP, ZO-1 (TJP1) and podocin, are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find that the nephrocyte diaphragm is completely lost in flies lacking the orthologues of nephrin or NEPH1—a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in human congenital nephrotic syndrome of the Finnish type, NPHS1) or NEPH1. These changes markedly impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting that the two cell types are evolutionarily related, and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-03-06 17:12
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