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Originally published In Press as doi:10.1074/jbc.M611403200 on February 21, 2007

J. Biol. Chem., Vol. 282, Issue 16, 12290-12297, April 20, 2007
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Apolipoprotein E Receptor-2 (ApoER2) Mediates Selenium Uptake from Selenoprotein P by the Mouse Testis*

Gary E. Olson{ddagger}1, Virginia P. Winfrey{ddagger}, Subir K. NagDas{ddagger}2, Kristina E. Hill§, and Raymond F. Burk§

From the {ddagger}Department of Cell and Developmental Biology and the §Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232

Selenium is a micronutrient that is essential for the production of normal spermatozoa. The selenium-rich plasma protein selenoprotein P (Sepp1) is required for maintenance of testis selenium and for fertility of the male mouse. Sepp1 trafficking in the seminiferous epithelium was studied using conventional methods and mice with gene deletions. Immunocytochemistry demonstrated that Sepp1 is present in vesicle-like structures in the basal region of Sertoli cells, suggesting that the protein is taken up intact. Sepp1 affinity chromatography of a testicular extract followed by mass spectrometry-based identification of bound proteins identified apolipoprotein E receptor 2 (ApoER2) as a candidate testis Sepp1 receptor. In situ hybridization analysis identified Sertoli cells as the only cell type in the seminiferous epithelium with detectable ApoER2 expression. Testis selenium levels in apoER2-/- males were sharply reduced from those in apoER2+/+ males and were comparable with the depressed levels found in Sepp1-/- males. However, liver selenium levels were unchanged by deletion of apoER2. Immunocytochemistry did not detect Sepp1 in the Sertoli cells of apoER2-/- males, consistent with a defect in the receptor-mediated Sepp1 uptake pathway. Phase contrast microscopy revealed identical sperm defects in apoER2-/- and Sepp1-/- mice. Co-immunoprecipitation analysis demonstrated an interaction of testis ApoER2 with Sepp1. These data demonstrate that Sertoli cell ApoER2 is a Sepp1 receptor and a component of the selenium delivery pathway to spermatogenic cells.


Received for publication, December 12, 2006 , and in revised form, February 20, 2007.

* This work was supported by National Institutes of Health Grants HD044863 and ES02497. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

2 Present address: Department of Natural Sciences, Fayetteville State University, Fayetteville, NC 28301.

1 To whom correspondence should be addressed: Dept. of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232-2175. Tel.: 615-322-0852; Fax: 615-343-9484; E-mail: gary.olson{at}vanderbilt.edu.




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