Editor-in-Chief: Brüne, Bernhard
Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred
SCImago Journal Rank (SJR) 2015: 1.607
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Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3Division of Gastroenterology, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA
4Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Citation Information: Biological Chemistry. Volume 390, Issue 1, Pages 67–73, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2009.011, November 2008
- Published Online:
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.
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