title: Nephrin phosphorylation regulates podocyte adhesion through the PINCH-1-ILK-α-parvin complex.
abstract: Nephrin, a structural molecule, is also a signaling molecule after phosphorylation. Inhibition of nephrin phosphorylation is correlated with podocyte injury. The PINCH-1-ILK-α-parvin (PIP) complex plays a crucial role in cell adhesion and cytoskeleton formation. We hypothesized that nephrin phosphorylation influenced cytoskeleton and cell adhesion in podocytes by regulating the PIP complex. The nephrin phosphorylation, PIP complex formation, and F-actin in Wistar rats intraperitoneally injected with puromycin aminonucleoside were gradually decreased but increased with time, coinciding with the recovery from glomerular/podocyte injury and proteinuria. In cultured podocytes, PIP complex knockdown resulted in cytoskeleton reorganization and decreased cell adhesion and spreading. Nephrin and its phosphorylation were unaffected after PIP complex knockdown. Furthermore, inhibition of nephrin phosphorylation suppressed PIP complex expression, disorganized podocyte cytoskeleton, and decreased cell adhesion and spreading. These findings indicate that alterations in nephrin phosphorylation disorganize podocyte cytoskeleton and decrease cell adhesion through a PIP complex-dependent mechanism.
authors.affiliation: Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zha
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Xinghua
authors.initials: X
authors.lastname: Chen
authors.forename: Tean
authors.initials: T
authors.lastname: Ma
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yang
authors.forename: Harry van
authors.initials: Hv
authors.lastname: Goor
authors.forename: Guohua
authors.initials: G
authors.lastname: Ding
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D060588:LIM Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000099200:Scaffold Protein ILK
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D011692:Puromycin Aminonucleoside; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK; C490232:Lims1 protein, mouse; C519774:Parva protein, mouse; C113267:nephrin