Renal uptake of the antiapoptotic protein survivin is mediated by megalin at the apical membrane of the proximal tubule

Jobst-Schwan T, Knaup K, Nielsen R, Hackenbeck T, Büttner-Herold M, Lechler P, Kroening S, Goppelt-Strübe M, Schlötzer-Schrehardt U, Fuernrohr BG, Voll RE, Amann KU, Eckardt KU, Christensen EI, Wiesener M (2013)

Publication Type: Journal article

Publication year: 2013

Journal

American Journal of Physiology-Renal Physiology American Physiological Society

Book Volume: 305

Pages Range: F734-F744

Journal Issue: 5

DOI: 10.1152/ajprenal.00546.2012

Abstract

The inhibitor of apoptosis protein survivin is a bifunctional molecule that regulates cellular division and survival. We have previously shown that survivin protein can be found at high concentrations in the adult kidney, particularly in the proximal tubules. Here, survivin is localized primarily at the apical membrane, a pattern that may indicate absorption of the protein. Several proteins in primary urine are internalized by megalin, an endocytosis receptor, which is in principle found in the same localization as survivin. Immunolabeling for survivin in different species confirmed survivin signal localizing to the apical membrane of the proximal tubule. Immunoelectron microscopy also showed apical localization of survivin in human kidneys. Furthermore, in polarized human primary tubular cells endogenous as well as external recombinant survivin is stored in the apical region of the cells. Costaining of survivin and megalin by immunohistochemistry and immunoelectron microscopy confirmed colocalization. Finally, by surface plasmon resonance we were able to demonstrate that survivin binds megalin and cubilin and that megalin knockout mice lose survivin through the urine. Survivin accumulates at the apical membrane of the renal tubule by reuptake, which is achieved by the endocytic receptor megalin, collaborating with cubilin. For this to occur, survivin will have to circulate in the blood and be filtered into the primary urine. It is not known at this stage what the functional role of tubular survivin is. However, a small number of experimental and clinical reports implicate that renal survivin is important for functional integrity of the kidney. © 2013 by the American Physiological Society.

Authors with CRIS profile

Tilman Jobst-Schwan Department of Medicine 4 – Nephrology and Hypertension Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Maike Büttner-Herold Medizinische Fakultät Margarete Goppelt-Strübe Department of Medicine 4 – Nephrology and Hypertension Ursula Schlötzer-Schrehardt Medizinische Fakultät Kerstin Ute Amann Department of Nephropathology Kai-Uwe Eckardt Department of Medicine 4 – Nephrology and Hypertension Michael Wiesener Professur für Innere Medizin (Nephrologie)

Involved external institutions

Aarhus University DK Denmark (DK) Universitätsklinikum Gießen und Marburg (UKGM) DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE)

How to cite

APA:

Jobst-Schwan, T., Knaup, K., Nielsen, R., Hackenbeck, T., Büttner-Herold, M., Lechler, P.,... Wiesener, M. (2013). Renal uptake of the antiapoptotic protein survivin is mediated by megalin at the apical membrane of the proximal tubule. American Journal of Physiology-Renal Physiology, 305(5), F734-F744. https://doi.org/10.1152/ajprenal.00546.2012

MLA:

Jobst-Schwan, Tilman, et al. "Renal uptake of the antiapoptotic protein survivin is mediated by megalin at the apical membrane of the proximal tubule." American Journal of Physiology-Renal Physiology 305.5 (2013): F734-F744.

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