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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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Volume 390, Issue 1 (Jan 2009)


Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling

Irene Masiulis
  • 1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
/ Timothy A. Quill
  • 2Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
/ Raymond F. Burk
  • 3Division of Gastroenterology, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
/ Joachim Herz
  • 4Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Published Online: 2008-11-13 | DOI: https://doi.org/10.1515/BC.2009.011


Apolipoprotein E receptor 2 (Apoer2) is a multifunctional transport and signaling receptor that regulates the uptake of selenium into the mouse brain and testis through endocytosis of selenoprotein P (Sepp1). Mice deficient in Apoer2 or Sepp1 are infertile, with kinked and hypomotile spermatozoa. They also develop severe neurological defects on a low selenium diet, due to a profound impairment of selenium uptake. Little is known about the function of Apoer2 in the testis beyond its role as a Sepp1 receptor. By contrast, in the brain, Apoer2 is an essential component of the Reelin signaling pathway, which is required for proper neuronal organization and synapse function. Using knock-in mice, we have functionally dissociated the signaling motifs in the Apoer2 cytoplasmic domain from Sepp1 uptake. Selenium concentration of brain and testis was normal in the knock-in mutants, in contrast to Apoer2 knock-outs. Thus, the neurological defects in the signaling impaired knock-in mice are not caused by a selenium uptake defect, but instead are a direct consequence of a disruption of the Reelin signal. Reduced sperm motility was observed in some of the knock-in mice, indicating a novel signaling role for Apoer2 in sperm development and function that is independent of selenium uptake.

Keywords: Disabled-1; LRP8; male fertility; Reelin; sperm motility; very-low-density lipoprotein receptor (VLDLR)

About the article

Corresponding author

Received: 2008-08-07

Accepted: 2008-10-14

Published Online: 2008-11-13

Published in Print: 2009-01-01

Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2009.011. Export Citation

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