The slit diaphragm in Drosophila exhibits a bilayered, fishnet architecture.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-01 DOI:10.1038/s41467-025-64347-5

Deborah Moser,Konrad Lang,Alexandra N Birtasu,Florian Grahammer,Martin Helmstädter,Margot P Scheffer,Tobias Hermle,Achilleas S Frangakis

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Abstract

The kidney relies on the glomerulus to filter large volumes of blood plasma, with the slit diaphragm (SD) as a key structural component of the glomerular filtration barrier. Despite its central role, the molecular architecture of the SD has remained elusive for decades. Using cryo-electron tomography on focused ion beam-milled Drosophila nephrocytes, an invertebrate podocyte model, we show that the SD exhibits a bilayered fishnet architecture. In the cryo-electron tomography map, we observe criss-crossing strands spanning the extracellular space that can be populated with Sns and Kirre, the Drosophila orthologs of nephrin and Neph1, respectively. We show that sns silencing shortens the SD lines until disappearance, linking the fishnet architecture directly to Sns. After Rab5 silencing, which causes Sns mistrafficking and ectopic formation of the SD, the fishnet pattern also appears ectopically. Elucidating the molecular SD architecture establishes a crucial link between the SD organization and its (patho)physiology.

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果蝇的狭缝隔膜呈双层鱼网状结构。

肾脏依靠肾小球过滤大量血浆，狭缝隔膜（SD）是肾小球滤过屏障的关键结构成分。尽管具有核心作用，但SD的分子结构几十年来一直难以捉摸。利用低温电子断层扫描对聚焦离子束磨磨的果蝇肾细胞（一种无脊椎动物足细胞模型）进行研究，我们发现果蝇肾细胞呈双层渔网结构。在低温电子断层扫描图中，我们观察到跨越细胞外空间的纵横交错的链，可以分别由sn和Kirre填充，它们是肾素和Neph1的果蝇同源物。我们发现sns沉默会缩短SD线直至消失，将渔网结构直接与sns联系起来。Rab5沉默后，导致Sns的误传递和SD的异位形成，鱼网型也出现异位。阐明SD分子结构在SD组织及其病理生理之间建立了重要的联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.