title: Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes.
abstract: BACKGROUND
  Podocytes serve as an important constituent of the glomerular filtration barrier. Recently, we and others identified Myo1e as a key molecular component of the podocyte cytoskeleton.
  
  
  RESULTS
  Myo1e mRNA and protein was expressed in human and mouse kidney sections as determined by Northern blot and reverse transcriptase PCR, and its expression was more evident in podocytes by immunofluorescence. By specific knock-down of MYO1E in zebrafish, the injected larvae exhibited pericardial edema and pronephric cysts, consistent with the appearance of protein in condensed incubation supernate. Furthermore, specific inhibition of Myo1e expression in a conditionally immortalized podocyte cell line induced morphological changes, actin cytoskeleton rearrangement, and dysfunction in cell proliferation, migration, endocytosis, and adhesion with the glomerular basement membrane.
  
  
  CONCLUSIONS
  Our results revealed that Myo1e is a key component contributing to the functional integrity of podocytes. Its impairment may cause actin cytoskeleton re-organization, alteration of cell shape, and membrane transport, and podocyte drop-out from the glomerular basement membrane, which might eventually lead to an impaired glomerular filtration barrier and proteinuria.
authors: Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, PR China. maojh88@gmail.com
authors: Jianhua
authors: J
authors: Mao
authors: Dayan
authors: D
authors: Wang
authors: Parikka
authors: P
authors: Mataleena
authors: Bing
authors: B
authors: He
authors: Dadi
authors: D
authors: Niu
authors: Kan
authors: K
authors: Katayama
authors: Xiangjun
authors: X
authors: Xu
authors: Juha Rm
authors: JR
authors: Ojala
authors: Wenjing
authors: W
authors: Wang
authors: Qiang
authors: Q
authors: Shu
authors: Lizhong
authors: L
authors: Du
authors: Aimin
authors: A
authors: Liu
authors: Timo
authors: T
authors: Pikkarainen
authors: Jaakko
authors: J
authors: Patrakka
authors: Karl
authors: K
authors: Tryggvason
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D054443:Cell Migration Assays; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D005306:Fertilization; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism; D051379:Mice; D024461:Myosin Type I / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D014168:Transferrin; D029961:Zebrafish Proteins; C000594664:myo1ea protein, zebrafish; C511011:MYO1E protein, human; C505821:Myo1e protein, mouse; D024461:Myosin Type I; D009218:Myosins; D016650:Fluorescein-5-isothiocyanate
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