Nephrin–Ephrin-B1–Na+/H+ Exchanger Regulatory Factor 2–Ezrin–Actin Axis Is Critical in Podocyte Injury

Ephrin-B1 is one of the critical components slit diaphragm kidney glomerular podocyte. However, precise function ephrin-B1 unclear. To clarify ephrin-B1, ephrin-B1–associated molecules were studied. RNA-sequencing analysis suggested that Na+/H+ exchanger regulatory factor 2 (NHERF2), a scaffolding protein, associated with ephrin-B1. NHERF2 was expressed at apical area and diaphragm, interacted nephrin–ephrin-B1 complex diaphragm. The nephrin–ephrin-B1–NHERF2 ezrin bound to F-actin. via its first postsynaptic density protein-95/disks large/zonula occludens-1 domain, podocalyxin second domain. Both in vitro analyses human embryonic 293 cells vivo study rat nephrotic model showed stimulaiton phosphorylation nephrin dephosphorylation ezrin, disrupted linkages ephrin-B1–NHERF2 NHERF2-ezrin. It conceivable linkage nephrin–ephrin-B1–NHERF2–ezrin–actin novel axis podocytes. also an transmembrane podocalyxin, NHERF2-ezrin-actin. consequent are initiation events leading podocyte injury. 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