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...
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| Veröffentlicht in: | The Journal of biological chemistry 2003-06, Vol.278 (26), p.23989-23995 |
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| container_title | The Journal of biological chemistry |
| container_volume | 278 |
| creator | Andersen, Olav M Yeung, Ching-Hei Vorum, Henrik Wellner, Maren Andreassen, Thomas K Erdmann, Bettina Mueller, Eva-Christina Herz, Joachim Otto, Albrecht Cooper, Trevor G Willnow, Thomas E |
| description | 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. |
| doi_str_mv | 10.1074/jbc.M302157200 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M302157200</identifier><identifier>PMID: 12695510</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Cell Size ; Clusterin ; Epididymis ; Glutathione Peroxidase ; Glycoproteins ; Infertility, Male - etiology ; LDL-Receptor Related Proteins ; Male ; Mice ; Mice, Knockout ; Molecular Chaperones ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Receptors, Lipoprotein - physiology ; Sperm Maturation ; Sperm Motility ; Spermatogenesis ; Spermatozoa - cytology ; Spermatozoa - growth & development</subject><ispartof>The Journal of biological chemistry, 2003-06, Vol.278 (26), p.23989-23995</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-b56ac19665a04f36d2f915e32b08ecbf199a5f4665e523c7fe887bc3fb57cd9c3</citedby><cites>FETCH-LOGICAL-c457t-b56ac19665a04f36d2f915e32b08ecbf199a5f4665e523c7fe887bc3fb57cd9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12695510$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Andersen, Olav M</creatorcontrib><creatorcontrib>Yeung, Ching-Hei</creatorcontrib><creatorcontrib>Vorum, Henrik</creatorcontrib><creatorcontrib>Wellner, Maren</creatorcontrib><creatorcontrib>Andreassen, Thomas K</creatorcontrib><creatorcontrib>Erdmann, Bettina</creatorcontrib><creatorcontrib>Mueller, Eva-Christina</creatorcontrib><creatorcontrib>Herz, Joachim</creatorcontrib><creatorcontrib>Otto, Albrecht</creatorcontrib><creatorcontrib>Cooper, Trevor G</creatorcontrib><creatorcontrib>Willnow, Thomas E</creatorcontrib><title>Essential Role of the Apolipoprotein E Receptor-2 in Sperm Development</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.</description><subject>Animals</subject><subject>Cell Size</subject><subject>Clusterin</subject><subject>Epididymis</subject><subject>Glutathione Peroxidase</subject><subject>Glycoproteins</subject><subject>Infertility, Male - etiology</subject><subject>LDL-Receptor Related Proteins</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Chaperones</subject><subject>Phospholipid Hydroperoxide Glutathione Peroxidase</subject><subject>Receptors, Lipoprotein - physiology</subject><subject>Sperm Maturation</subject><subject>Sperm Motility</subject><subject>Spermatogenesis</subject><subject>Spermatozoa - cytology</subject><subject>Spermatozoa - growth & development</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1LAzEQxYMotlavHmUP4m1rPjab5Fhqq0JFqArewm46cbfsNmuyVfzvjbTQo3MZZub3HsND6JLgMcEiu12XZvzEMCVcUIyP0JBgyVLGyfsxGuK4TxXlcoDOQljjWJkip2hAaK44J3iI5rMQYNPXRZMsXQOJs0lfQTLpXFN3rvOuh3qTzJIlGOh651OaxPmlA98md_AFjevaqD9HJ7ZoAlzs-wi9zWev04d08Xz_OJ0sUpNx0aclzwtDVJ7zAmeW5StqFeHAaIklmNISpQpus3gHTpkRFqQUpWG25MKslGEjdLPzjZ99biH0uq2DgaYpNuC2QQvGZCaJ_BckUkilaB7B8Q403oXgwerO123hfzTB-i9iHSPWh4ij4GrvvC1bWB3wfaYRuN4BVf1RfdcedFk7U0GrqZCa5poyJRX7BdSrgko</recordid><startdate>20030627</startdate><enddate>20030627</enddate><creator>Andersen, Olav M</creator><creator>Yeung, Ching-Hei</creator><creator>Vorum, Henrik</creator><creator>Wellner, Maren</creator><creator>Andreassen, Thomas K</creator><creator>Erdmann, Bettina</creator><creator>Mueller, Eva-Christina</creator><creator>Herz, Joachim</creator><creator>Otto, Albrecht</creator><creator>Cooper, Trevor G</creator><creator>Willnow, Thomas E</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030627</creationdate><title>Essential Role of the Apolipoprotein E Receptor-2 in Sperm Development</title><author>Andersen, Olav M ; Yeung, Ching-Hei ; Vorum, Henrik ; Wellner, Maren ; Andreassen, Thomas K ; Erdmann, Bettina ; Mueller, Eva-Christina ; Herz, Joachim ; Otto, Albrecht ; Cooper, Trevor G ; Willnow, Thomas E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-b56ac19665a04f36d2f915e32b08ecbf199a5f4665e523c7fe887bc3fb57cd9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Cell Size</topic><topic>Clusterin</topic><topic>Epididymis</topic><topic>Glutathione Peroxidase</topic><topic>Glycoproteins</topic><topic>Infertility, Male - etiology</topic><topic>LDL-Receptor Related Proteins</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Chaperones</topic><topic>Phospholipid Hydroperoxide Glutathione Peroxidase</topic><topic>Receptors, Lipoprotein - physiology</topic><topic>Sperm Maturation</topic><topic>Sperm Motility</topic><topic>Spermatogenesis</topic><topic>Spermatozoa - cytology</topic><topic>Spermatozoa - growth & development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Andersen, Olav M</creatorcontrib><creatorcontrib>Yeung, Ching-Hei</creatorcontrib><creatorcontrib>Vorum, Henrik</creatorcontrib><creatorcontrib>Wellner, Maren</creatorcontrib><creatorcontrib>Andreassen, Thomas K</creatorcontrib><creatorcontrib>Erdmann, Bettina</creatorcontrib><creatorcontrib>Mueller, Eva-Christina</creatorcontrib><creatorcontrib>Herz, Joachim</creatorcontrib><creatorcontrib>Otto, Albrecht</creatorcontrib><creatorcontrib>Cooper, Trevor G</creatorcontrib><creatorcontrib>Willnow, Thomas E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Andersen, Olav M</au><au>Yeung, Ching-Hei</au><au>Vorum, Henrik</au><au>Wellner, Maren</au><au>Andreassen, Thomas K</au><au>Erdmann, Bettina</au><au>Mueller, Eva-Christina</au><au>Herz, Joachim</au><au>Otto, Albrecht</au><au>Cooper, Trevor G</au><au>Willnow, Thomas E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Essential Role of the Apolipoprotein E Receptor-2 in Sperm Development</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2003-06-27</date><risdate>2003</risdate><volume>278</volume><issue>26</issue><spage>23989</spage><epage>23995</epage><pages>23989-23995</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><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.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>12695510</pmid><doi>10.1074/jbc.M302157200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2003-06, Vol.278 (26), p.23989-23995 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Cell Size Clusterin Epididymis Glutathione Peroxidase Glycoproteins Infertility, Male - etiology LDL-Receptor Related Proteins Male Mice Mice, Knockout Molecular Chaperones Phospholipid Hydroperoxide Glutathione Peroxidase Receptors, Lipoprotein - physiology Sperm Maturation Sperm Motility Spermatogenesis Spermatozoa - cytology Spermatozoa - growth & development |
| title | Essential Role of the Apolipoprotein E Receptor-2 in Sperm Development |
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