Essential Role of the Apolipoprotein E Receptor-2 in Sperm Development
Open accessAbstract
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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ApoE and ApoJ are known ligands for VLDLR.
“Both ApoE and ApoJ (also called Clusterin)–two apolipoproteins found in cerebrospinal fluid–are known ligands for VLDLR26,53,54.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [26]
Cites
Hiesberger, T., Trommsdorff, M., Howell, B. W., Goffinet, A., Mumby, M. C., Cooper, J. A., & Herz, J. (1999) · Neuron · doi:10.1016/s0896-6273(00)80861-2 · Cited by 916 · see citing works
Self-citationThe reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2
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More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158 · see citing works
Self-citationFunctional Roles of the Interaction of APP and Lipoprotein Receptors
Pohlkamp, T., Wasser, C. R., & Herz, J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00054 · Cited by 92 · see citing works
Self-citationIDOL regulates systemic energy balance through control of neuronal VLDLR expression
Lee, S. D., Priest, C., Bjursell, M., Gao, J., Arneson, D. V., Ahn, I. S., Diamante, G., van Veen, J. E., Massa, M. G., Calkin, A. C., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0127-7 · Cited by 26 · see citing works
- Authors
- Andersen, O. M., Yeung, C.-H., Vorum, H., Wellner, M., Andreassen, T. K., Erdmann, B., Mueller, E.-C., Herz, J., Otto, A., Cooper, T. G., & Willnow, T. E.
- Affiliations
- Max Delbrück Center (DE)
- University of Münster (DE)
- Aarhus University (DK)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Willnow, Thomas E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-06
- Volume
- 278
- Issue
- 26
- Pages
- 23989-23995
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2153605568
- Cited by
- 112
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 2 · 2015: 5 · 2014: 9 · 2013: 2 · 2012: 7
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R37HL063762)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Keywords
- ApoER2, sperm development, sperm maturation, epididymis, clusterin, phospholipid hydroperoxide glutathione peroxidase, male infertility, sperm motility, sperm morphology, LDL receptor family
- MeSH terms
- Phospholipid Hydroperoxide Glutathione Peroxidase, Reelin Protein, Animals, Epididymis, Glutathione Peroxidase, Glycoproteins, Infertility, Male, Male, Sperm Maturation, Sperm Motility, Spermatogenesis, Spermatozoa, Receptors, Lipoprotein, Mice, Knockout, Molecular Chaperones, LDL-Receptor Related Proteins, Cell Size, Clusterin, Mice
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