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 Citations (Scopus)

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

Fingerprint

Cell signaling
Selenium
Testis
Brain
Defects
Spermatozoa
Selenoprotein P
Sperm Motility
Nutrition
Endocytosis
low density lipoprotein receptor-related protein 8
Synapses
Diet

Keywords

  • Disabled-1
  • LRP8
  • Male fertility
  • Reelin
  • Sperm motility
  • Very-low-density lipoprotein receptor (VLDLR)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology

Cite this

Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. / Masiulis, Irene; Quill, Timothy A.; Burk, Raymond F.; Herz, Joachim.

In: Biological Chemistry, Vol. 390, No. 1, 01.01.2009, p. 67-73.

Research output: Contribution to journalArticle

Masiulis, Irene ; Quill, Timothy A. ; Burk, Raymond F. ; Herz, Joachim. / Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling. In: Biological Chemistry. 2009 ; Vol. 390, No. 1. pp. 67-73.
@article{7bfd0bbc0c1043049594ba8cce8d6e9d,
title = "Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling",
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.",
keywords = "Disabled-1, LRP8, Male fertility, Reelin, Sperm motility, Very-low-density lipoprotein receptor (VLDLR)",
author = "Irene Masiulis and Quill, {Timothy A.} and Burk, {Raymond F.} and Joachim Herz",
year = "2009",
month = "1",
day = "1",
doi = "10.1515/BC.2009.011",
language = "English (US)",
volume = "390",
pages = "67--73",
journal = "Biological Chemistry",
issn = "1431-6730",
publisher = "Walter de Gruyter GmbH & Co. KG",
number = "1",

}

TY - JOUR

T1 - Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling

AU - Masiulis, Irene

AU - Quill, Timothy A.

AU - Burk, Raymond F.

AU - Herz, Joachim

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - Disabled-1

KW - LRP8

KW - Male fertility

KW - Reelin

KW - Sperm motility

KW - Very-low-density lipoprotein receptor (VLDLR)

UR - http://www.scopus.com/inward/record.url?scp=58249107850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58249107850&partnerID=8YFLogxK

U2 - 10.1515/BC.2009.011

DO - 10.1515/BC.2009.011

M3 - Article

C2 - 19007311

AN - SCOPUS:58249107850

VL - 390

SP - 67

EP - 73

JO - Biological Chemistry

JF - Biological Chemistry

SN - 1431-6730

IS - 1

ER -