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

First Author  Masiulis I Year  2009
Journal  Biol Chem Volume  390
Issue  1 Pages  67-73
PubMed ID  19007311 Mgi Jnum  J:153933
Mgi Id  MGI:4366625 Doi  10.1515/BC.2009.011
Citation  Masiulis I, et al. (2009) Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. Biol Chem 390(1):67-73
abstractText  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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