Abstract
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.
Original language | English (US) |
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Pages (from-to) | 67-73 |
Number of pages | 7 |
Journal | Biological Chemistry |
Volume | 390 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2009 |
Keywords
- Disabled-1
- LRP8
- Male fertility
- Reelin
- Sperm motility
- Very-low-density lipoprotein receptor (VLDLR)
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Clinical Biochemistry