Sorting Nexin 9 Facilitates Podocin Endocytosis in the Injured Podocyte

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 8

PMID 28266622

Citations 5

Authors

Yu Sasaki

Teruo Hidaka

Takashi Ueno

Miyuki Akiba-Takagi

Juan Alejandro Oliva Trejo

Takuto Seki

Yoshiko Nagai-Hosoe

Eriko Tanaka

Satoshi Horikoshi

Yasuhiko Tomino

Yusuke Suzuki

Katsuhiko Asanuma

Affiliations

Soon will be listed here.

Abstract

The irreversibility of glomerulosclerotic changes depends on the degree of podocyte injury. We have previously demonstrated the endocytic translocation of podocin to the subcellular area in severely injured podocytes and found that this process is the primary disease trigger. Here we identified the protein sorting nexin 9 (SNX9) as a novel facilitator of podocin endocytosis in a yeast two-hybrid analysis. SNX9 is involved in clathrin-mediated endocytosis, actin rearrangement and vesicle transport regulation. Our results revealed and confirmed that SNX9 interacts with podocin exclusively through the Bin-Amphiphysin-Rvs (BAR) domain of SNX9. Immunofluorescence staining revealed the expression of SNX9 in response to podocyte adriamycin-induced injury both in vitro and in vivo. Finally, an analysis of human glomerular disease biopsy samples demonstrated strong SNX9 expression and co-localization with podocin in samples representative of severe podocyte injury, such as IgA nephropathy with poor prognosis, membranous nephropathy and focal segmental glomerulosclerosis. In conclusion, we identified SNX9 as a facilitator of podocin endocytosis in severe podocyte injury and demonstrated the expression of SNX9 in the podocytes of both nephropathy model mice and human patients with irreversible glomerular disease.

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