C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation.

Abstract	Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions.
Authors	Jiyoun Lee, Ara Koh, Heeyoon Jeong, Eui Kim, Tae-Sun Ha, Moin A Saleem, Sung Ho Ryu
Journal	Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 12346 (09 27 2017) ISSN: 2045-2322 [Electronic] England
PMID	28955049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	IRS1 protein, human Insulin Receptor Substrate Proteins Membrane Proteins Tensins nephrin Phosphatidylinositol 3-Kinases Mechanistic Target of Rapamycin Complex 1 TNS2 protein, human Tns2 protein, mouse Protein Tyrosine Phosphatases Glucose
Topics	Animals Diabetic Nephropathies (pathology) Glucose (metabolism) HEK293 Cells Humans Hypertrophy (pathology) Insulin Receptor Substrate Proteins (metabolism) Male Mechanistic Target of Rapamycin Complex 1 (metabolism) Membrane Proteins (metabolism) Mice Phosphatidylinositol 3-Kinases (metabolism) Phosphorylation Podocytes (pathology) Protein Tyrosine Phosphatases (metabolism) Proteinuria (etiology, pathology) Signal Transduction Tensins (metabolism)

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