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SIRPalpha interacts with nephrin at the podocyte slit diaphragm.

Authors: Kajiho, Y  Harita, Y  Kurihara, H  Horita, S  Matsunaga, A  Tsurumi, H  Kanda, S  Sugawara, N  Miura, K  Sekine, T  Hattori, S  Hattori, M  Igarashi, T 
Citation: Kajiho Y, etal., FEBS J. 2012 Sep;279(17):3010-21. doi: 10.1111/j.1742-4658.2012.08682.x. Epub 2012 Jul 23.
Pubmed: (View Article at PubMed) PMID:22747997
DOI: Full-text: DOI:10.1111/j.1742-4658.2012.08682.x

The slit diaphragm (SD) is an intercellular junction between renal glomerular epithelial cells (podocytes) that is essential for permselectivity in glomerular ultrafiltration. The SD components, nephrin and Neph1, assemble a signaling complex in a tyrosine phosphorylation dependent manner, and regulate the unique actin cytoskeleton of podocytes. Mutations in the NPHS1 gene that encodes nephrin cause congenital nephrotic syndrome (CNS), which is characterized by the loss of the SD and massive proteinuria. Recently, we have identified the expression of the transmembrane glycoprotein signal regulatory protein alpha (SIRPalpha) at the SD. In the present study, we analyzed the expression of SIRPalpha in developing kidneys, in kidneys from CNS patients and in proteinuric rat models. The possibility that SIRPalpha interacts with known SD proteins was also investigated. SIRPalpha was concentrated at the SD junction during the maturation of intercellular junctions. In the glomeruli of CNS patients carrying mutations in NPHS1, where SD formation is disrupted, the expression of SIRPalpha as well as Neph1 and nephrin was significantly decreased, indicating that SIRPalpha is closely associated with the nephrin complex. Indeed, SIRPalpha formed hetero-oligomers with nephrin in cultured cells and in glomeruli. Furthermore, the cytoplasmic domain of SIRPalpha was highly phosphorylated in normal glomeruli, and its phosphorylation was dramatically decreased upon podocyte injury in vivo. Thus, SIRPalpha interacts with nephrin at the SD, and its phosphorylation is dynamically regulated in proteinuric states. Our data provide new molecular insights into the phosphorylation events triggered by podocyte injury.


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CRRD Object Information
CRRD ID: 8553639
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.