Article
Developmental Biology
Alexandra Atienza-Manuel, Vicente Castillo-Mancho, Stefano De Renzis, Joaquim Culi, Mar Ruiz-Gomez
Summary: The complex composed of Amnionless, Cubilin, and Cubilin2 is crucial for nephrocyte slit diaphragm (SD) dynamics in Drosophila. Loss of CUBAM-mediated endocytosis leads to dramatic morphological changes in nephrocytes and mislocalisation of SD, likely due to an imbalance between endocytosis and exocytosis. While rescuing receptor-mediated endocytosis can partially restore SD positioning in CUBAM mutants, suggesting a specific requirement of CUBAM in SD degradation and recycling.
Article
Urology & Nephrology
Johanna Odenthal, Sebastian Dittrich, Vivian Ludwig, Tim Merz, Katrin Reitmeier, Bjoern Reusch, Martin Hoehne, Zuelfue C. Cosgun, Maximilian Hohenadel, Jovana Putnik, Heike Goebel, Markus M. Rinschen, Janine Altmueller, Sybille Koehler, Bernhard Schermer, Thomas Benzing, Bodo B. Beck, Paul T. Brinkkoetter, Sandra Habbig, Malte P. Bartram
Summary: This study reports a case of a 4-year-old boy with proteinuria and biopsy-proven focal segmental glomerulosclerosis (FSGS). Molecular genetic testing identified a novel mutation in alpha-actinin-4 that is associated with the disease. The study showed that the mutation led to decreased stability of alpha-actinin-4, protein mislocalization, and cytoskeleton rearrangements. Using a Drosophila model, the researchers demonstrated the pathogenicity of the mutation.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Cell Biology
Dominik Spitz, Maria Comas, Lea Gerstner, Severine Kayser, Martin Helmstaedter, Gerd Walz, Tobias Hermle
Summary: Both mTOR signaling and autophagy play important roles in regulating podocyte homeostasis, regeneration, and aging, as well as in glomerular diseases. This study used Drosophila nephrocytes as a podocyte model and found that inhibition of mTOR signaling led to increased spacing between slit diaphragms. Activation or inhibition of mTOR signaling both resulted in decreased nephrocyte function, indicating a delicate balance of signaling activity is required for proper function. Furthermore, mTOR positively regulated cell size, survival, and the subcortical actin network, while basal autophagy in nephrocytes was necessary for survival and limited the expression of nephrin, but did not directly affect slit diaphragm formation or endocytic activity. Excessive, mTOR-dependent autophagy was primarily responsible for slit diaphragm misspacing. Overall, this study established an invertebrate podocyte model for exploring the role of mTOR signaling and autophagy, and revealed a direct regulation of slit diaphragm architecture by the mTOR/autophagy pathway.
Article
Biology
Kiyoung Kim, Sun Joo Cha, Hyun-Jun Choi, Jeong Suk Kang, Eun Young Lee
Summary: In this study, a Drosophila model of diabetic nephropathy was established by feeding flies a chronic high-sucrose diet, which led to reduced lifespan, increased lipid droplets, and morphological abnormalities in nephrocytes. The high-sucrose diet also induced mitochondrial fusion in nephrocytes. These findings suggest that Drosophila can serve as a valuable model for studying the pathogenesis and treatment of DN.
Article
Cell Biology
Ismael Morin-Poulard, Manon Destalminil-Letourneau, Laetitia Bataille, Jean-Louis Frendo, Gaelle Lebreton, Nathalie Vanzo, Michele Crozatier
Summary: This study investigates the ontogeny of the posterior lobes of the Drosophila lymph gland during larval development and identifies the genetic basis of this process. The posterior lobes are found to originate from embryonic pericardial cells, and their composition of blood progenitors is progressively built during larval development. Homeotic genes and the transcription factor Klf15 are found to regulate the fate choice between blood cell and nephrocyte in larvae.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Urology & Nephrology
Lea Gerstner, Mengmeng Chen, Lina L. Kampf, Julian Milosavljevic, Konrad Lang, Ronen Schneider, Friedhelm Hildebrandt, Martin Helmstaedter, Gerd Walz, Tobias Hermle
Summary: Risk variants of the APOL1 gene are associated with severe kidney disease. By using the Drosophila model, researchers have found that the expression of APOL1 risk variants leads to cell death and endoplasmic reticulum stress response, shedding light on the pathogenesis of APOL1-associated nephropathies.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Vanessa Krausel, Lisanne Pund, Harald Nuesse, Hussein Bachir, Andrea Ricker, Jurgen Klingauf, Thomas Weide, Hermann Pavenstaedt, Michael P. Krahn, Daniela A. Braun
Summary: Mutations in OSGEP and four other genes that encode subunits of the KEOPS complex cause Galloway-Mowat syndrome, a severe, inherited kidney-neurological disease. Here, the researchers investigated the molecular pathogenic mechanisms of KEOPS-related glomerular disease and found that ATF4-mediated signaling is a molecular link among ER stress, slit diaphragm defects, and podocyte injury. Modulation of ATF4 signaling may be a potential therapeutic target for certain podocyte diseases.
KIDNEY INTERNATIONAL
(2023)
Review
Pediatrics
Sybille Koehler, Tobias B. Huber
Summary: Biological and biomedical research using fruit flies as a model organism has been highly recognized and even awarded with several Nobel prizes. The advantages of fruit flies over other in vivo models, such as short life cycle, easy and inexpensive animal maintenance, and availability of various transgenic strains and tools, make them a preferred choice. Additionally, fruit flies have a high degree of conservation with human genes, providing valuable insights into human diseases. This article specifically focuses on the use of fruit flies in nephrology research, highlighting the significance of studying kidney tissues and the potential of nephrocytes in understanding inter-organ communication and kidney function.
PEDIATRIC NEPHROLOGY
(2023)
Article
Developmental Biology
Marta Carrasco-Rando, Joaquim Culi, Sonsoles Campuzano, Mar Ruiz-Gomez
Summary: The assembly of slit diaphragms in Drosophila embryonic garland nephrocytes is facilitated by a cell division that breaks membrane symmetry and generates PIP2-enriched domains at the equator. This allows for the recruitment and assembly of slit diaphragm proteins, leading to the formation of functional nephrocytes.
Article
Biochemistry & Molecular Biology
Luyao Wang, Pei Wen, Joyce van de Leemput, Zhanzheng Zhao, Zhe Han
Summary: By using Drosophila nephrocytes as a genetic screen platform, this study identified key components of the SD protein endocytosis and recycling pathway, highlighting their importance in maintaining the filtration structure. The findings demonstrate that the components in this pathway are highly conserved and play a role in the endocytosis and recycling of SD proteins in human kidney, suggesting mutations in these genes could lead to renal diseases.
CELL AND BIOSCIENCE
(2021)
Article
Cell Biology
Mee-Ling Maywald, Cara Picciotto, Carolin Lepa, Luisa Bertgen, Farwah Sanam Yousaf, Andrea Ricker, Jurgen Klingauf, Michael P. Krahn, Hermann Pavenstadt, Britta George
Summary: The study reveals that Rap1 plays a crucial role in maintaining the filtration function of glomerular podocytes and the integrity of slit diaphragms, and it regulates these processes by mediating the signal transduction between nephrin and integrin beta.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Urology & Nephrology
Julian Milosavljevic, Camille Lempicki, Konrad Lang, Helena Heinkele, Lina L. Kampf, Claire Leroy, Mengmeng Chen, Lea Gerstner, Dominik Spitz, Minxian Wang, Andrea U. Knob, Severine Kayser, Martin Helmstadter, Gerd Walz, Martin R. Pollak, Tobias Hermle
Summary: Background variants in TBC1D8B cause nephrotic syndrome by affecting nephrin trafficking and podocyte function. The study found that a null allele of the fruit fly TBC1D8B gene resulted in mislocalization of nephrin in nephrocytes, similar to patients with isolated nephrotic syndrome. TBC1D8B was shown to be essential for rapid turnover and endocytosis of nephrin, as well as for endosomal cargo processing and degradation. Additionally, four novel TBC1D8B variants were discovered in a cohort of FSGS patients, highlighting the importance of TBC1D8B in FSGS.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bayan Kharrat, Gabor Csordas, Viktor Honti
Summary: The fruit fly, Drosophila melanogaster, has been a valuable model organism for studying hematopoiesis regulation. The lymph gland of the fly larva exhibits similar features and functions to the hematopoietic stem cell niche in vertebrates. The use of advanced tools in Drosophila research has allowed for a detailed understanding of the cellular composition and regulatory networks in the lymph gland.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Qianqian Ge, Jiajia Wang, Jitao Li, Jian Li
Summary: High alkalinity stress was found to inhibit ion transport function of pillar cells and induce the active role of nephrocytes in alkalinity adaptation in Exopa-laemon carinicauda. Single-cell RNA sequencing showed differential expression of genes related to ion transport in pillar cells and nephrocytes.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Pediatrics
Agnieszka Bierzynska, Katherine Bull, Sara Miellet, Philip Dean, Chris Neal, Elizabeth Colby, Hugh J. McCarthy, Shivaram Hegde, Manish D. Sinha, Carmen Bugarin Diz, Kathleen Stirrups, Karyn Megy, Rutendo Mapeta, Chris Penkett, Sarah Marsh, Natalie Forrester, Maryam Afzal, Hannah Stark, Nihr BioResource, Maggie Williams, Gavin Welsh, Ania B. Koziell, Paul S. Hartley, Moin A. Saleem
Summary: Variants in NUP93 gene have been identified as a cause of paediatric SRNS. In this study, NUP93 variants were detected in paediatric onset SRNS patients and the functional effects of Nup93 depletion were demonstrated in a fly nephrocyte model.
PEDIATRIC NEPHROLOGY
(2022)