title: Schip1 is a novel podocyte foot process protein that mediates actin cytoskeleton rearrangements and forms a complex with Nherf2 and ezrin.
abstract: 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.
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
authors: Ljubica
authors: L
authors: Perisic
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Patricia Q
authors: PQ
authors: Rodriguez
authors: Clinical Research Center, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Kjell
authors: K
authors: Hultenby
authors: Vascular Biology Division, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Ying
authors: Y
authors: Sun
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Mark
authors: M
authors: Lal
authors: Vascular Biology Division, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Christer
authors: C
authors: Betsholtz
authors: Department of Biotechnology, Royal Institute of Technology, Stockholm, Sweden.
authors: Mathias
authors: M
authors: Uhlén
authors: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
authors: Annika
authors: A
authors: Wernerson
authors: Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
authors: Ulf
authors: U
authors: Hedin
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Timo
authors: T
authors: Pikkarainen
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Karl
authors: K
authors: Tryggvason
authors: Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Jaakko
authors: J
authors: Patrakka
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D060910:Pronephros / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D053778:Thiazolidines / Q000494:pharmacology; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000099149:Ezrin
chemical_list: D000199:Actins; D000077214:Becaplermin; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D015638:Cytochalasin D; D003598:Cytoskeletal Proteins; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D020574:Proto-Oncogene Proteins c-sis; D017923:Sodium-Hydrogen Exchangers; D053778:Thiazolidines; D029961:Zebrafish Proteins; D000099149:Ezrin; C405019:SCHIP1 protein, human; C093376:sodium-hydrogen exchanger regulatory factor; C037067:latrunculin A