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. 2022 Oct 20;20:480. doi: 10.1186/s12967-022-03706-y

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Dysfunction of Cubilin induced by the variants locating after vitB12-binding domain of CUBN was accompanied by abnormal localization of AMN. A The protein expression of Cubilin and Megalin in kidney tissues was detected by immunofluorescence assay and showed the expression and localization of Megalin did not accompany the decrease of Cubilin expression. B Immunofluorescence staining showed the decrease expression of Cubilin caused by the CUBN variant was accompanied by aberrant cytoplasmic localization of AMN in renal tubule membrane. C and D Representative photomicrographs by TEM analyses confirmed the GFB damage and immunofluorescence staining were to detect the colocalization and expression between Cubilin and AMN in kidney biopsies from MCD and FSGS. E and F The reduced expression of renal Cubilin was not accompanied by abnormal localization of AMN in the mice model of LPS-induced acute kidney injury and Adriamycin-induced nephropathy. Each group was tested in triplicate, and the data are given data are presented as the mean ± S.D. ns, no significant; *P < 0.05; **P < 0.01; ***P < 0.001