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The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm

Nature volume 457, pages 322–326 (2009)Cite this article

Abstract

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.

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Figure 1: The glomerular and nephrocyte filtration barriers are anatomically similar.
Figure 2: Sns and Duf are expressed in Drosophila nephrocytes.
Figure 3: Sns and Duf are required for nephrocyte diaphragm formation and normal morphology.
Figure 4: Analysis of slit-diaphragm-associated protein orthologues in the fly nephrocyte.
Figure 5: Sns and Duf are required for nephrocyte filtration.

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Acknowledgements

We thank F. Evers, Z. Cseresnyes, M. Guerra and E. Salvador for technical assistance, and S. Abmayr, L. Cooley, C. Doe, M. Affolter, K. Fischbach and K. Tryggvason for reagents. We thank V. Hartenstein, M. Inamdar, A. Woolf, I. Miguel-Aliaga, F. Evers, M. Landgraf and members of the Skaer laboratory for discussions, and E. Knust and W. B. Huttner for their support. This work was supported by Wellcome Trust grants awarded to H.S. (072441 and 079221; H.W., B.D. and H.S.); Deutsche Forschungsgemeinschaft SFB 590 awarded to E. Knust (F.G.) and ARC 1242 (H.W., B.D., H.S. and F.G.); an MEC grant awarded to M.R.-G. (BFU2007-62201; S.P.-S. and M.R.-G.); a Fundación Ramón Areces grant to the CBMSO (M.R.-G.); EC grant LSHG-CT-2004-511978 to MYORES (M.R.-G.); and an FPU fellowship from the MEC awarded to A.G.-L.

Author Contributions B.D., H.S. and M.R.-G. designed and directed the project. B.D., H.W., M.R.-G. and S.P.-S. performed the experiments. F.G. and M.W.-B. provided technical assistance. A.G.-L. and R.A. provided materials. B.D. and H.S. wrote the paper. All authors discussed results and commented on the manuscript.

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Author notes

  1. Helen Weavers and Silvia Prieto-Sánchez: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK,

    Helen Weavers, Helen Skaer & Barry Denholm

  2. Centro de Biología Molecular Severo Ochoa, CSIC, UAM, Cantoblanco, 28049 Madrid, Spain ,

    Silvia Prieto-Sánchez & Mar Ruiz-Gómez

  3. Institut für Genetik, Heinrich-Heine-Universität, Düsseldorf D-40225, Germany ,

    Ferdinand Grawe

  4. Department of Genetics, University of Valencia, Burjasot, Valencia 46100, Spain,

    Amparo Garcia-López & Ruben Artero

  5. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden D-01307, Germany

    Michaela Wilsch-Bräuninger

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Correspondence to Helen Skaer.

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Weavers, H., Prieto-Sánchez, S., Grawe, F. et al. The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm. Nature 457, 322–326 (2009). https://doi.org/10.1038/nature07526

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