Lack of megalin expression in adult human terminal ileum suggests megalin‐independent cubilin/amnionless activity during vitamin B12 absorption

Physiological Reports

Louise L. Jensen²  Rikke K. Andersen²  Henrik Hager¹ 

[1] Department of Pathology, Aarhus University Hospital, Denmark;Department of Biomedicine, University of Aarhus, Denmark

关键词: Amnionless;    cubilin;    human terminal ileum;    megalin;    vitamin B12 absorption;   

DOI  :  10.14814/phy2.12086

来源: Wiley

【 摘 要 】

Abstract

Cubilin plays an essential role in terminal ileum and renal proximal tubules during absorption of vitamin B₁₂ and ligands from the glomerular ultrafiltrate. Cubilin is coexpressed with amnionless, and cubilin and amnionless are mutually dependent on each other for correct processing to the plasma membrane upon synthesis. Patients with defects in either protein suffer from vitamin B₁₂-malabsorption and in some cases proteinuria. Cubilin lacks a transmembrane region and signals for endocytosis and is dependent on a transmembrane coreceptor during internalization. Amnionless has been shown to be able to mediate internalization of cubilin in a cell-based model system. Cubilin has additionally been suggested to function together with megalin, and a recent study of megalin-deficient patients indicates that uptake of cubilin ligands in the kidney is critically dependent on megalin. To further investigate the potential role of amnionless and megalin in relation to cubilin function in terminal ileum and vitamin B₁₂ uptake, we initiated a study of CUBN/cubilin, AMN/amnionless, and LRP2/megalin expression in adult human terminal ileum. Our study is the first to reveal the expression pattern of cubilin, amnionless, and megalin in adult human terminal ileum, where cubilin and amnionless localize to the epithelial cells. Surprisingly, we did not detect any megalin protein in adult terminal ileum and consistently, only extremely low amounts of LRP2 mRNA. Our data therefore advocate that cubilin and amnionless act independently of megalin in adult terminal ileum and that the cubilin-megalin interdependency accordingly should be considered as tissue and ligand specific.

【 授权许可】

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© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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