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http://dx.doi.org/10.5483/BMBRep.2013.46.4.270

Nephrin phosphorylation regulates podocyte adhesion through the PINCH-1-ILK-α-parvin complex  

Zha, Dongqing (Division of Nephrology, Renmin Hospital of Wuhan University)
Chen, Cheng (Division of Nephrology, Renmin Hospital of Wuhan University)
Liang, Wei (Division of Nephrology, Renmin Hospital of Wuhan University)
Chen, Xinghua (Division of Nephrology, Renmin Hospital of Wuhan University)
Ma, Tean (Division of Nephrology, Renmin Hospital of Wuhan University)
Yang, Hongxia (Division of Nephrology, Renmin Hospital of Wuhan University)
van Goor, Harry (Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen)
Ding, Guohua (Division of Nephrology, Renmin Hospital of Wuhan University)
Publication Information
BMB Reports / v.46, no.4, 2013 , pp. 230-235 More about this Journal
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-${\alpha}$-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.
Keywords
Cell adhesion; Nephrin phosphorylation; PINCH-1-ILK-${\alpha}$-parvin complex; Podocyte;
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