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Essential role of the apolipoprotein E receptor-2 in sperm development

Item Type:Article
Title:Essential role of the apolipoprotein E receptor-2 in sperm development
Creators Name:Andersen, O.M., Yeung, C.H., Vorum, H., Wellner, M., Andreassen, T.K., Erdmann, B., Mueller, E.C., Herz, J., Otto, A., Cooper, T.G. and Willnow, T.E.
Abstract:The apolipoprotein (apo) E receptor-2 (apoER2) is a member of the low density lipoprotein receptor gene family and an important regulator of neuronal migration. It acts as a receptor for the signaling factor Reelin and provides positional cues to neurons that migrate to their proper position in the developing brain. Besides brain formation defects, apoER2-deficient mice also exhibit male infertility. The role of the receptor in male reproduction, however, remained unclear. Here we demonstrate that apoER2 is highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. Reduced PHGPx expression in apoER2 knockout mice results in the inability of the sperm to regulate the cell volume and in abnormal sperm morphology and immotility. Because insufficient expression of PHGPx is a major cause of infertility in men, these findings not only highlight an important new function for apoER2 that is unrelated to neuronal migration, but they also suggest a possible role for apoER2 in human infertility.
Keywords:Cell Size, Clusterin, Epididymis, Glutathione Peroxidase, Glycoproteins, Knockout Mice, Lipoprotein Receptors, Male Infertility, Molecular Chaperones, Sperm Maturation, Sperm Motility, Spermatogenesis, Spermatozoa, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology
Volume:278
Number:26
Page Range:23989-23995
Date:27 June 2003
Official Publication:https://doi.org/10.1074/jbc.M302157200
PubMed:View item in PubMed

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