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

Olav M. Andersen, Ching Hei Yeung, Henrik Vorum, Maren Wellner, Thomas K. Andreassen, Bettina Erdmann, Eva Christina Mueller, Joachim Herz, Albrecht Ott, Trevor G. Coopers, Thomas E. Willnow

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)23989-23995
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number26
DOIs
StatePublished - Jul 27 2003

Fingerprint

Apolipoprotein E2
Low Density Lipoprotein Receptor-Related Protein-1
phospholipid-hydroperoxide glutathione peroxidase
Spermatozoa
Infertility
Brain
Sperm Maturation
Clusterin
LDL Receptors
Epididymis
Male Infertility
Cell Size
Knockout Mice
Neurons
Cues
Reproduction
Genes
low density lipoprotein receptor-related protein 8
Defects
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Andersen, O. M., Yeung, C. H., Vorum, H., Wellner, M., Andreassen, T. K., Erdmann, B., ... Willnow, T. E. (2003). Essential role of the apolipoprotein E receptor-2 in sperm development. Journal of Biological Chemistry, 278(26), 23989-23995. https://doi.org/10.1074/jbc.M302157200

Essential role of the apolipoprotein E receptor-2 in sperm development. / Andersen, Olav M.; Yeung, Ching Hei; Vorum, Henrik; Wellner, Maren; Andreassen, Thomas K.; Erdmann, Bettina; Mueller, Eva Christina; Herz, Joachim; Ott, Albrecht; Coopers, Trevor G.; Willnow, Thomas E.

In: Journal of Biological Chemistry, Vol. 278, No. 26, 27.07.2003, p. 23989-23995.

Research output: Contribution to journalArticle

Andersen, OM, Yeung, CH, Vorum, H, Wellner, M, Andreassen, TK, Erdmann, B, Mueller, EC, Herz, J, Ott, A, Coopers, TG & Willnow, TE 2003, 'Essential role of the apolipoprotein E receptor-2 in sperm development', Journal of Biological Chemistry, vol. 278, no. 26, pp. 23989-23995. https://doi.org/10.1074/jbc.M302157200
Andersen OM, Yeung CH, Vorum H, Wellner M, Andreassen TK, Erdmann B et al. Essential role of the apolipoprotein E receptor-2 in sperm development. Journal of Biological Chemistry. 2003 Jul 27;278(26):23989-23995. https://doi.org/10.1074/jbc.M302157200
Andersen, Olav M. ; Yeung, Ching Hei ; Vorum, Henrik ; Wellner, Maren ; Andreassen, Thomas K. ; Erdmann, Bettina ; Mueller, Eva Christina ; Herz, Joachim ; Ott, Albrecht ; Coopers, Trevor G. ; Willnow, Thomas E. / Essential role of the apolipoprotein E receptor-2 in sperm development. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 26. pp. 23989-23995.
@article{34c3df5663874cca86bbc98739c1b0a1,
title = "Essential role of the apolipoprotein E receptor-2 in sperm development",
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.",
author = "Andersen, {Olav M.} and Yeung, {Ching Hei} and Henrik Vorum and Maren Wellner and Andreassen, {Thomas K.} and Bettina Erdmann and Mueller, {Eva Christina} and Joachim Herz and Albrecht Ott and Coopers, {Trevor G.} and Willnow, {Thomas E.}",
year = "2003",
month = "7",
day = "27",
doi = "10.1074/jbc.M302157200",
language = "English (US)",
volume = "278",
pages = "23989--23995",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

TY - JOUR

T1 - Essential role of the apolipoprotein E receptor-2 in sperm development

AU - Andersen, Olav M.

AU - Yeung, Ching Hei

AU - Vorum, Henrik

AU - Wellner, Maren

AU - Andreassen, Thomas K.

AU - Erdmann, Bettina

AU - Mueller, Eva Christina

AU - Herz, Joachim

AU - Ott, Albrecht

AU - Coopers, Trevor G.

AU - Willnow, Thomas E.

PY - 2003/7/27

Y1 - 2003/7/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0038606196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038606196&partnerID=8YFLogxK

U2 - 10.1074/jbc.M302157200

DO - 10.1074/jbc.M302157200

M3 - Article

C2 - 12695510

AN - SCOPUS:0038606196

VL - 278

SP - 23989

EP - 23995

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -