title: Cubilin and amnionless mediate protein reabsorption in Drosophila nephrocytes.
abstract: The insect nephrocyte and the mammalian glomerular podocyte are similar with regard to filtration, but it remains unclear whether there is an organ or cell type in flies that reabsorbs proteins. Here, we show that the Drosophila nephrocyte has molecular, structural, and functional similarities to the renal proximal tubule cell. We screened for genes required for nephrocyte function and identified two Drosophila genes encoding orthologs of mammalian cubilin and amnionless (AMN), two major receptors for protein reabsorption in the proximal tubule. In Drosophila, expression of dCubilin and dAMN is specific to nephrocytes, where they function as co-receptors for protein uptake. Targeted expression of human AMN in Drosophila nephrocytes was sufficient to rescue defective protein uptake induced by dAMN knockdown, suggesting evolutionary conservation of Cubilin/AMN co-receptors function from flies to humans. Furthermore, we found that Cubilin/AMN-mediated protein reabsorption is required for the maintenance of nephrocyte ultrastructure and fly survival under conditions of toxic stress. In conclusion, the insect nephrocyte combines filtration with protein reabsorption, using evolutionarily conserved genes and subcellular structures, suggesting that it can serve as a simplified model for both podocytes and the renal proximal tubule.
authors.affiliation: Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Fujian
authors.initials: F
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yufang
authors.initials: Y
authors.lastname: Chao
authors.forename: Katherine
authors.initials: K
authors.lastname: Muir
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008317:Malpighian Tubules / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*
chemical_list: C484714:AMN protein, human; C579277:Cubn protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D011506:Proteins; D011956:Receptors, Cell Surface; C093565:amn protein, Drosophila; C029486:intrinsic factor-cobalamin receptor; D049452:Green Fluorescent Proteins