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

Irene Masiulis, Timothy A. Quill, Raymond F. Burk, Joachim Herz

Research output: Contribution to journalArticle

20 Scopus citations

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 languageEnglish (US)
Pages (from-to)67-73
Number of pages7
JournalBiological Chemistry
Volume390
Issue number1
DOIs
StatePublished - 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

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