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The Insect Nephrocyte Is A Podocyte-like Cell With A Filtration Slit Diaphragm

机译:昆虫肾细胞是具有过滤缝膜片的足细胞样细胞

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The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultra-filtration, 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 melano-gaster) 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.
机译:肾单位是脊椎动物肾脏的基本结构和功能单位。它由肾小球,超滤部位和肾小管组成,沿这些肾小管对滤液进行修饰。尽管被广泛认为是脊椎动物的适应动物1,但在许多无脊椎动物的排泄系统中仍会发现“类肾单位”的特征,这增加了脊椎动物排泄系统的组成部分是从其无脊椎动物祖先那里继承来的可能性2。在这里,我们显示昆虫肾细胞与肾小球足细胞具有显着的解剖,分子和功能相似性,肾小球足细胞是脊椎动物肾脏中的细胞,随着血液被超滤以产生尿液,它形成了主要的尺寸选择屏障。特别地,两种细胞类型都具有专门的过滤膜片,在足细胞中称为狭缝膜片,在肾细胞中称为肾细胞膜片。我们发现,裂膜的主要成分,包括nephrin,NEPH1(也称为KIRREL),CD2AP,ZO-1(TJP1)和podocin的蝇(果蝇)直向同源物在肾细胞中表达并形成相互作用蛋白的复合物,与脊椎动物的缝隙隔膜复合物紧密相像。此外,我们发现,在缺乏肾素或NEPH1-直系同源物的果蝇中,肾细胞膜完全消失,类似于缺乏肾素(如人类先天性肾病综合征,芬兰型,NPHS1)或裂隙膜的丧失。 NEPH1。这些变化明显损害肾细胞的过滤功能。我们描述的无脊椎动物肾细胞和脊椎动物足细胞之间的相似性提供了证据,表明这两种细胞类型在进化上相关,并将肾细胞建立为研究足细胞生物学和足细胞相关疾病的简单模型。

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