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Gene expression analysis defines the proximal tubule as the compartment for endocytic receptor-mediated uptake in the Xenopus pronephric kidney

  • Molecular and Genomic Physiology
  • Published:
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Abstract

Endocytic receptors in the proximal tubule of the mammalian kidney are responsible for the reuptake of numerous ligands, including lipoproteins, sterols, vitamin-binding proteins, and hormones, and they can mediate drug-induced nephrotoxicity. In this paper, we report the first evidence indicating that the pronephric kidneys of Xenopus tadpoles are capable of endocytic transport. We establish that the Xenopus genome harbors genes for the known three endocytic receptors megalin/LRP2, cubilin, and amnionless. The Xenopus endocytic receptor genes share extensive synteny with their mammalian counterparts. In situ hybridizations demonstrated that endocytic receptor expression is highly tissue specific, primarily in the pronephric kidney, and did not occur prior to neurulation. Expression was strictly confined to proximal tubules of the pronephric kidney, which closely resembles the situation reported in mammalian kidneys. By immunohistochemistry, we demonstrated that Xenopus pronephric tubule epithelia express high amounts of the endocytic receptors megalin/lrp2 and cubilin in the apical plasma membrane. Furthermore, functional aspects of the endocytic receptors were revealed by the vesicular localization of retinol-binding protein in the proximal tubules, probably representing endocytosed protein. In summary, we provide here the first comprehensive report of endocytic receptor expression, including amnionless, in a nonmammalian species. Remarkably, renal endocytic receptor expression and function in the Xenopus pronephric kidney closely mirrors the situation in the mammalian kidney. The Xenopus pronephric kidney therefore represents a novel, simple model for physiological studies on the molecular mechanisms underlying renal tubular endocytosis.

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Acknowledgements

We thank Hanne Sidelmann and Inger Kristoffersen for skilful technical assistance. The work was supported in part by the Danish Medical Research Council, the University of Aarhus, the NOVO-Nordisk Foundation, and the Biomembrane Research Center to EIC, the ETH Zürich and the Swiss National Science Foundation (3100A0-101964) to AWB, and the European Community (EuReGene LSHG-CT-2004-005085) to EIC, PJV, and AWB.

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  1. Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

    Erik I. Christensen

  2. Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, Switzerland

    Daniela Raciti, Luca Reggiani & André W. Brändli

  3. INSERM U538, Centre Hospitalier Universitaire, Saint Antoine, Paris, France

    Pierre J. Verroust

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  1. Erik I. Christensen
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Christensen, E.I., Raciti, D., Reggiani, L. et al. Gene expression analysis defines the proximal tubule as the compartment for endocytic receptor-mediated uptake in the Xenopus pronephric kidney. Pflugers Arch - Eur J Physiol 456, 1163–1176 (2008). https://doi.org/10.1007/s00424-008-0488-3

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