Essential role of the apolipoprotein E receptor-2 in sperm development.
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.
Andersen
Olav M
OM
Max-Delbrueck-Center for Molecular Medicine and Medical Faculty of the Free University, D-13125 Berlin, Germany.
Yeung
Ching-Hei
CH
Vorum
Henrik
H
Wellner
Maren
M
Andreassen
Thomas K
TK
Erdmann
Bettina
B
Mueller
Eva-Christina
EC
Herz
Joachim
J
Otto
Albrecht
A
Cooper
Trevor G
TG
Willnow
Thomas E
TE
D000818:Animals; D048429:Cell Size; D051152:Clusterin; D004822:Epididymis; D005979:Glutathione Peroxidase; D006023:Glycoproteins; D007248:Infertility, Male / Q000209:etiology; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D018110:Receptors, Lipoprotein / Q000502:physiology*; D000091042:Reelin Protein; D013079:Sperm Maturation; D013081:Sperm Motility; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development
C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D026502:LDL-Receptor Related Proteins; D018832:Molecular Chaperones; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C098773:low density lipoprotein receptor-related protein 8; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C000717127:RELN protein, human; C000717128:Reln protein, mouse