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.
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U2 - 10.1074/jbc.M302157200
DO - 10.1074/jbc.M302157200
M3 - Article
C2 - 12695510
AN - SCOPUS:0038606196
SN - 0021-9258
VL - 278
SP - 23989
EP - 23995
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -