title: The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm.
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 adaptation, '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 ancestors. 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.
authors.affiliation: Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Weavers
authors.forename: Silvia
authors.initials: S
authors.lastname: Prieto-Sánchez
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Grawe
authors.forename: Amparo
authors.initials: A
authors.lastname: Garcia-López
authors.forename: Ruben
authors.initials: R
authors.lastname: Artero
authors.forename: Michaela
authors.initials: M
authors.lastname: Wilsch-Bräuninger
authors.forename: Mar
authors.initials: M
authors.lastname: Ruiz-Gómez
authors.forename: Helen
authors.initials: H
authors.lastname: Skaer
authors.forename: Barry
authors.initials: B
authors.lastname: Denholm
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000166:cytology* / Q000502:physiology; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; D009124:Muscle Proteins; C410904:SNS protein, Drosophila; C413082:kirre protein, Drosophila; C113267:nephrin