Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies

Development
Antonio S TutorMar Ruiz-Gómez

Abstract

Drosophila nephrocytes are functionally homologous to vertebrate kidney podocytes. Both share the presence of slit diaphragms that function as molecular filters during the process of blood and haemolymph ultrafiltration. The protein components of the slit diaphragm are likewise conserved between flies and humans, but the mechanisms that regulate slit diaphragm dynamics in response to injury or nutritional changes are still poorly characterised. Here, we show that Dumbfounded/Neph1, a key diaphragm constituent, is a target of the Src kinase Src64B. Loss of Src64B activity leads to a reduction in the number of diaphragms, and this effect is in part mediated by loss of Dumbfounded/Neph1 tyrosine phosphorylation. The phosphorylation of Duf by Src64B, in turn, regulates Duf association with the actin regulator Dock. We also find that diaphragm damage induced by administration of the drug puromycin aminonucleoside (PAN model) directly associates with Src64B hyperactivation, suggesting that diaphragm stability is controlled by Src-dependent phosphorylation of diaphragm components. Our findings indicate that the balance between diaphragm damage and repair is controlled by Src-dependent phosphorylation of diaphragm components, and point...Continue Reading

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Citations

Apr 13, 2017·Cell and Tissue Research·Martin Helmstädter, Matias Simons
Jan 31, 2018·Journal of Cellular Biochemistry·Florian HochapfelMichael P Krahn
Jun 7, 2019·The Journal of Cell Biology·Marta Carrasco-RandoMar Ruiz-Gómez
Jun 30, 2018·BioMed Research International·Cassandra Millet-BoureimaChiara Gamberi
Jun 6, 2020·Journal of Cell Science·Lena DehnenAchim Paululat
Dec 10, 2016·Journal of the American Society of Nephrology : JASN·Tobias HermleFriedhelm Hildebrandt
Apr 12, 2016·Journal of Cardiovascular Development and Disease·Barbara Rotstein, Achim Paululat
Jul 19, 2017·Cellular and Molecular Life Sciences : CMLS·Florian HochapfelMichael P Krahn
Dec 23, 2017·Frontiers in Pediatrics·Martin HelmstädterTobias Hermle
Nov 17, 2020·Cell and Tissue Research·Takayuki MiyakiKoichiro Ichimura
Apr 3, 2021·Journal of the American Society of Nephrology : JASN·Michael Mysh, John S Poulton

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