Schip1 Is a Novel Podocyte Foot Process Protein that Mediates Actin Cytoskeleton Rearrangements and Forms a Complex with Nherf2 and Ezrin
| Autor: | Jaakko Patrakka, Annika Wernerson, Kjell Hultenby, Mathias Uhlén, Patricia Q. Rodriguez, Timo Pikkarainen, Ying Sun, Christer Betsholtz, Mark Lal, Ljubica Perisic, Karl Tryggvason, Ulf Hedin |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cytochalasin D
Sodium-Hydrogen Exchangers Kidney Glomerulus Becaplermin lcsh:Medicine macromolecular substances Biology Pronephros chemistry.chemical_compound Ezrin Cell Movement Fluorescence Resonance Energy Transfer Animals Humans Pseudopodia Cytoskeleton lcsh:Science Cells Cultured Zebrafish Actin Multidisciplinary Podocytes HEK 293 cells lcsh:R Correction Proto-Oncogene Proteins c-sis Oligonucleotides Antisense Zebrafish Proteins Bridged Bicyclo Compounds Heterocyclic Phosphoproteins Actin cytoskeleton Molecular biology Actins Cell biology Actin Cytoskeleton Cytoskeletal Proteins HEK293 Cells Microscopy Fluorescence chemistry Thiazolidines RNA Interference lcsh:Q Signal transduction Carrier Proteins Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 5, p e0126079 (2015) PLoS ONE, Vol 10, Iss 3, p e0122067 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Background Podocyte foot process effacement accompanied by actin cytoskeleton rearrangements is a cardinal feature of many progressive human proteinuric diseases. Results By microarray profiling of mouse glomerulus, SCHIP1 emerged as one of the most highly enriched transcripts. We detected Schip1 protein in the kidney glomerulus, specifically in podocytes foot processes. Functionally, Schip1 inactivation in zebrafish by morpholino knock-down results in foot process disorganization and podocyte loss leading to proteinuria. In cultured podocytes Schip1 localizes to cortical actin-rich regions of lamellipodia, where it forms a complex with Nherf2 and ezrin, proteins known to participate in actin remodeling stimulated by PDGFβ signaling. Mechanistically, overexpression of Schip1 in vitro causes accumulation of cortical F-actin with dissolution of transversal stress fibers and promotes cell migration in response to PDGF-BB stimulation. Upon actin disassembly by latrunculin A treatment, Schip1 remains associated with the residual F-actin-containing structures, suggesting a functional connection with actin cytoskeleton possibly via its interaction partners. A similar assay with cytochalasin D points to stabilization of cortical actin cytoskeleton in Schip1 overexpressing cells by attenuation of actin depolymerisation. Conclusions Schip1 is a novel glomerular protein predominantly expressed in podocytes, necessary for the zebrafish pronephros development and function. Schip1 associates with the cortical actin cytoskeleton network and modulates its dynamics in response to PDGF signaling via interaction with the Nherf2/ezrin complex. Its implication in proteinuric diseases remains to be further investigated. |
| Databáze: | OpenAIRE |
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