Actin Cytoskeleton and Integrin Components Are Interdependent for Slit Diaphragm Maintenance in Drosophila Nephrocytes

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-08, Vol.13 (16), p.1350
• Main Authors: Delaney, Megan, Zhao, Yunpo, van de Leemput, Joyce, Lee, Hangnoh, Han, Zhe
• Format: Article
• Language: English
• Subjects: Actin; actin cytoskeleton; Actin Cytoskeleton - metabolism; Actins - metabolism; Animals; Antibodies; Basement membranes; Cytoskeleton; Drosophila; Drosophila - metabolism; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Females; Filtration; Flow cytometry; Genes; Genomes; Immunoglobulins; Insects; integrin; Integrins; Integrins - metabolism; Internalization; Kidney diseases; Laboratories; lacunar channel; nephrocyte; Nephrotic syndrome; Podocytes - metabolism; RNA-mediated interference; slit diaphragm; Structure-function relationships
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13161350

In nephrotic syndrome, the podocyte filtration structures are damaged in a process called foot process effacement. This is mediated by the actin cytoskeleton; however, which actins are involved and how they interact with other filtration components, like the basement membrane, remains poorly understood. Here, we used the well-established pericardial nephrocyte-the equivalent of podocytes in flies-knockdown models (RNAi) to study the interplay of the actin cytoskeleton (Act5C, Act57B, Act42A, and Act87E), alpha- and beta-integrin (basement membrane), and the slit diaphragm (Sns and Pyd). Knockdown of an actin gene led to variations of formation of actin stress fibers, the internalization of Sns, and a disrupted slit diaphragm cortical pattern. Notably, deficiency of , which resulted in complete absence of nephrocytes, could be partially mitigated by overexpressing or , suggesting at least partial functional redundancy. Integrin localized near the actin cytoskeleton as well as slit diaphragm components, but when the nephrocyte cytoskeleton or slit diaphragm was disrupted, this switched to colocalization, both at the surface and internalized in aggregates. Altogether, the data show that the interdependence of the slit diaphragm, actin cytoskeleton, and integrins is key to the structure and function of the nephrocyte.