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
Urology & Nephrology
Veniamin Ivanov, Yoshiyasu Fukusumi, Ying Zhang, Hidenori Yasuda, Meiko Kitazawa, Hiroshi Kawachi
Summary: Synbindin, identified as an important molecule in glomeruli, shows altered expression in various nephrotic models before traditional markers like nephrin. Its downregulation is associated with slit diaphragm dysfunction, affecting podocyte morphology and the expression of slit diaphragm-related proteins.
AMERICAN JOURNAL OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Kevin Gilhaus, Claudia Cepok, David Kamm, Beate Surmann, Pavel I. Nedvetsky, Jana Emich, Alina Sundukova, Katharina Saatkamp, Harald Nuesse, Juergen Klingauf, Dirk O. Wennmann, Britta George, Michael P. Krahn, Hermann-Joseph Pavenstaedt, Beate A. Vollenbroeker
Summary: Research has shown that Ajuba proteins regulate the connection between the slit diaphragm protein complex and the actin cytoskeleton in nephrocytes, while maintaining the Hippo pathway in an inactive state. Activation of the Hippo pathway reduces the level of Djub, while reducing Djub levels activates the Hippo pathway and leads to morphological changes in the slit diaphragm and increased permeability.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
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
Haijiao Zhang, Lin Lin, Jianping Liu, Lifeng Pan, Zhijie Lin, Mingjie Zhang, Jiong Zhang, Ying Cao, Jinwei Zhu, Rongguang Zhang
Summary: The slit diaphragm is a specialized adhesion junction that forms the final filtration barrier in the kidney. Key components at the slit diaphragm can spontaneously undergo phase separation, driving the formation of highly dense condensates and recruitment of adhesion molecules. Mutations in these components can lead to impaired formation of slit diaphragm condensates and enrichment of key proteins, ultimately impacting kidney function.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Hiroyuki Yamada, Naritoshi Shirata, Shinichi Makino, Takafumi Miyake, Juan Alejandro Oliva Trejo, Kanae Yamamoto-Nonaka, Mitsuhiro Kikyo, Maulana A. Empitu, Ika N. Kadariswantiningsih, Maiko Kimura, Koichiro Ichimura, Hideki Yokoi, Masashi Mukoyama, Akitsu Hotta, Katsuhiko Nishimori, Motoko Yanagita, Katsuhiko Asanuma
Summary: Podocytes play a crucial role in regulating the localization of Nephrin and Neph1, with MAGI-2 being essential for maintaining the integrity of the glomerular filtration barrier. Downregulation of MAGI-2 leads to reduced expression of slit-diaphragm backbone proteins, while its overexpression preserves their localization at intercellular junctions. The PDZ domains of MAGI-2 play a significant role in interacting with slit diaphragm backbone proteins in podocytes, suggesting a mechanism by which these proteins are maintained in their proper locations.
KIDNEY INTERNATIONAL
(2021)
Review
Medicine, Research & Experimental
Elham Ahmadian, Aziz Eftekhari, Seyyeddin Atakishizada, Mahbuba Valiyeva, Mohammadreza Ardalan, Rovshan Khalilov, Taras Kavetskyy
Summary: Renal injury and the development of albuminuria are closely connected to the loss of podocytes. Podocyte damages cause proteinuric renal diseases, with the rearrangement of the podocyte actin cytoskeleton being a chief mechanism. The molecular design and regulation of actin are important in podocyte research.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Urology & Nephrology
Chengqing Qu, Robyn Roth, Pongpratch Puapatanakul, Charles Loitman, Dina Hammad, Guy M. Genin, Jeffrey H. Miner, Hani Y. Suleiman
Summary: A new visualization technique has been developed to reveal the detailed three-dimensional organization of actin networks in healthy podocytes, providing insights into how podocytes respond to mechanical cues from their surrounding environment.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maximilian M. Gass, Sarah Borkowsky, Marie-Luise Lotz, Rebecca Siwek, Rita Schroeter, Pavel Nedvetsky, Stefan Luschnig, Astrid Rohlmann, Markus Missler, Michael P. Krahn
Summary: Drosophila nephrocytes, similar to mammalian podocytes, exhibit characteristics of epithelial cells. Research has shown that phospholipid PI(4,5)P2 plays a crucial role in slit diaphragm formation, while PI(3,4,5)P3 has minimal impact on nephrocyte function.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Susan T. Veissi, Tijmen van den Berge, Joanna A. E. van Wijk, Thea van der Velden, Rene Classens, Lynn Lunsonga, Rick Brockotter, Charlotte Kaffa, Sander Bervoets, Bart Smeets, Lambertus P. W. J. van den Heuvel, Michiel F. Schreuder
Summary: Levamisole exerts beneficial effects on podocytes in iNS by stabilizing the actin cytoskeleton in a glucocorticoid receptor-dependent manner.
Article
Biochemistry & Molecular Biology
Stefanie Heiden, Rebecca Siwek, Marie-Luise Lotz, Sarah Borkowsky, Rita Schroeter, Pavel Nedvetsky, Astrid Rohlmann, Markus Missler, Michael P. Krahn
Summary: The study revealed that in Drosophila nephrocytes, the apical-basal polarity regulators play a crucial role in regulating the morphology and assembly/maintenance of slit diaphragms, with distinct functions in endocytosis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Physiology
Qing Ye, Bing Lan, Huihui Liu, Pontus B. Persson, En Yin Lai, Jianhua Mao
Summary: This article discusses the mechanism of selective glomerular filtration, with a focus on the role of podocytes and the regulation of actin cytoskeleton in maintaining the integrity of the filtration barrier. The study found the presence of autoimmune podocytopathies in children with idiopathic nephrotic syndrome, revealing a new subgroup of the disease.
Article
Genetics & Heredity
Magdalena Patrycja Woznowski, Sebastian Alexander Potthoff, Eva Koenigshausen, Raphael Haase, Henning Hoch, Catherine Meyer-Schwesinger, Thorsten Wiech, Johannes Stegbauer, Lars Christian Rump, Lorenz Sellin, Ivo Quack
Summary: Chronic hyperglycemia, such as in diabetes mellitus, can lead to early signs of glomerular damage with microalbuminuria. Even acute hyperglycemia can increase glomerular permeability before structural damage occurs. A deeper understanding of the molecular mechanisms of albuminuria is desired. P38 MAPK signaling is involved in the development of hyperglycemia-induced albuminuria. Acute hyperglycemia triggers endocytosis of nephrin, the key molecule of the slit diaphragm.
JOURNAL OF MOLECULAR MEDICINE-JMM
(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)
Article
Urology & Nephrology
Annika Moller-Kerutt, Juan E. Rodriguez-Gatica, Karin Wacker, Rohan Bhatia, Jan-Peter Siebrasse, Nanda Boon, Veerle Van Marck, Peter Boor, Ulrich Kubitscheck, Jan Wijnholds, Hermann Pavenstadt, Thomas Weide
Summary: Mutations in the CRB2 gene can cause SRNS, and CRB2 is an essential component of podocyte slit diaphragm, interacting with Nephrin. Crb2(podKO) mice exhibit proteinuria, disordered foot processes, and increased renal injury and inflammatory markers.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)