Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO
In mammalian reproduction, testis-specific protein IZUMO1 and its receptor JUNO on the oocyte surface are essential for sperm-oocyte recognition, binding, and membrane fusion. However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic p...
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Veröffentlicht in: | Theriogenology 2025-01, Vol.231, p.160-170 |
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description | In mammalian reproduction, testis-specific protein IZUMO1 and its receptor JUNO on the oocyte surface are essential for sperm-oocyte recognition, binding, and membrane fusion. However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic proteins interact with them to facilitate sperm-oocyte interaction on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. In this study, Copper Transport Protein 2 (CTR2) has been identified on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. CTR2 directly interacts with both IZUMO1 and JUNO, colocalizing with IZUMO1 on the sperm head and with JUNO on the oocyte membrane. Treatment of the capacitated sperm and zona pellucida-free oocytes with anti-CTR2 antibody resulted in a significant decrease in fertilization rates in IVF experiments. These findings suggest that CTR2 plays an important role in mammalian fertilization by interacting with IZUMO1 and JUNO, providing new insights into the molecular mechanisms of mammalian sperm-oocyte adhesion and fusion. |
doi_str_mv | 10.1016/j.theriogenology.2024.10.016 |
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However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic proteins interact with them to facilitate sperm-oocyte interaction on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. In this study, Copper Transport Protein 2 (CTR2) has been identified on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. CTR2 directly interacts with both IZUMO1 and JUNO, colocalizing with IZUMO1 on the sperm head and with JUNO on the oocyte membrane. Treatment of the capacitated sperm and zona pellucida-free oocytes with anti-CTR2 antibody resulted in a significant decrease in fertilization rates in IVF experiments. These findings suggest that CTR2 plays an important role in mammalian fertilization by interacting with IZUMO1 and JUNO, providing new insights into the molecular mechanisms of mammalian sperm-oocyte adhesion and fusion.</description><identifier>ISSN: 0093-691X</identifier><identifier>ISSN: 1879-3231</identifier><identifier>EISSN: 1879-3231</identifier><identifier>DOI: 10.1016/j.theriogenology.2024.10.016</identifier><identifier>PMID: 39454481</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>adhesion ; animal reproduction ; Animals ; antibodies ; Cation Transport Proteins - genetics ; Cation Transport Proteins - metabolism ; cell membranes ; copper ; Copper Transport Proteins - metabolism ; CTR2 ; Female ; Fertilization - physiology ; head ; Immunoglobulins - metabolism ; IZUMO1 ; JUNO ; Male ; membrane fusion ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; oocytes ; Oocytes - metabolism ; Oocytes - physiology ; Protein-protein interaction ; Rats ; Sperm-egg fusion ; Sperm-Ovum Interactions - physiology ; spermatozoa ; Spermatozoa - metabolism ; Spermatozoa - physiology ; transport proteins</subject><ispartof>Theriogenology, 2025-01, Vol.231, p.160-170</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c290t-5b2ff2fa7fcd6c2438e53e3358c5d86073ac10be9c7756dfcb35311abc36a2683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0093691X24004308$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39454481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Rina</creatorcontrib><creatorcontrib>Liu, Ruizhuo</creatorcontrib><creatorcontrib>Sun, Yangyang</creatorcontrib><creatorcontrib>Su, Huimin</creatorcontrib><creatorcontrib>Xing, Wanjin</creatorcontrib><title>Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO</title><title>Theriogenology</title><addtitle>Theriogenology</addtitle><description>In mammalian reproduction, testis-specific protein IZUMO1 and its receptor JUNO on the oocyte surface are essential for sperm-oocyte recognition, binding, and membrane fusion. However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic proteins interact with them to facilitate sperm-oocyte interaction on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. In this study, Copper Transport Protein 2 (CTR2) has been identified on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. CTR2 directly interacts with both IZUMO1 and JUNO, colocalizing with IZUMO1 on the sperm head and with JUNO on the oocyte membrane. Treatment of the capacitated sperm and zona pellucida-free oocytes with anti-CTR2 antibody resulted in a significant decrease in fertilization rates in IVF experiments. These findings suggest that CTR2 plays an important role in mammalian fertilization by interacting with IZUMO1 and JUNO, providing new insights into the molecular mechanisms of mammalian sperm-oocyte adhesion and fusion.</description><subject>adhesion</subject><subject>animal reproduction</subject><subject>Animals</subject><subject>antibodies</subject><subject>Cation Transport Proteins - genetics</subject><subject>Cation Transport Proteins - metabolism</subject><subject>cell membranes</subject><subject>copper</subject><subject>Copper Transport Proteins - metabolism</subject><subject>CTR2</subject><subject>Female</subject><subject>Fertilization - physiology</subject><subject>head</subject><subject>Immunoglobulins - metabolism</subject><subject>IZUMO1</subject><subject>JUNO</subject><subject>Male</subject><subject>membrane fusion</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>oocytes</subject><subject>Oocytes - metabolism</subject><subject>Oocytes - physiology</subject><subject>Protein-protein interaction</subject><subject>Rats</subject><subject>Sperm-egg fusion</subject><subject>Sperm-Ovum Interactions - physiology</subject><subject>spermatozoa</subject><subject>Spermatozoa - metabolism</subject><subject>Spermatozoa - physiology</subject><subject>transport proteins</subject><issn>0093-691X</issn><issn>1879-3231</issn><issn>1879-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1OGzEUhS0EgjTtKyAvWNDFpP4Ze2YkNigqhQqIhIhUdWN5PHcSp5Px1HZSwdPXaaASO1a2_J3jo3sPQmeUTCih8stqEpfgrVtA7zq3eJowwvKEJgkeoBEtiyrjjNNDNCKk4pms6I8T9CGEFSGES0mP0QmvcpHnJR2hXw86YuOGATyOXvdhcD7iwbsItscMn08fH9hnbAO2_dZ1W2jSBbfgo-3ss47W9TguvdsslglE8Nr8e_tj4xLf_JzfzSjWfYO_z-9nH9FRq7sAn17OMZpffX2cXme3s28308vbzLCKxEzUrG1Zq4vWNNKwnJcgOHAuSiOaUpKCa0NJDZUpCiGb1tRccEp1bbjUTJZ8jM73_6Yxfm8gRLW2wUDX6R7cJihORU6FJLl8h5RRIqoiJYzRxV5qvAvBQ6sGb9faPylK1K4ZtVJvm1G7ZnY0wWQ_fUna1Gto_ptfq0iCq70A0mq2FrwKxkJvoLEeTFSNs-9L-gtREagz</recordid><startdate>20250101</startdate><enddate>20250101</enddate><creator>Su, Rina</creator><creator>Liu, Ruizhuo</creator><creator>Sun, Yangyang</creator><creator>Su, Huimin</creator><creator>Xing, Wanjin</creator><general>Elsevier Inc</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>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20250101</creationdate><title>Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO</title><author>Su, Rina ; Liu, Ruizhuo ; Sun, Yangyang ; Su, Huimin ; Xing, Wanjin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c290t-5b2ff2fa7fcd6c2438e53e3358c5d86073ac10be9c7756dfcb35311abc36a2683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>adhesion</topic><topic>animal reproduction</topic><topic>Animals</topic><topic>antibodies</topic><topic>Cation Transport Proteins - genetics</topic><topic>Cation Transport Proteins - metabolism</topic><topic>cell membranes</topic><topic>copper</topic><topic>Copper Transport Proteins - metabolism</topic><topic>CTR2</topic><topic>Female</topic><topic>Fertilization - physiology</topic><topic>head</topic><topic>Immunoglobulins - metabolism</topic><topic>IZUMO1</topic><topic>JUNO</topic><topic>Male</topic><topic>membrane fusion</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>oocytes</topic><topic>Oocytes - metabolism</topic><topic>Oocytes - physiology</topic><topic>Protein-protein interaction</topic><topic>Rats</topic><topic>Sperm-egg fusion</topic><topic>Sperm-Ovum Interactions - physiology</topic><topic>spermatozoa</topic><topic>Spermatozoa - metabolism</topic><topic>Spermatozoa - physiology</topic><topic>transport proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Rina</creatorcontrib><creatorcontrib>Liu, Ruizhuo</creatorcontrib><creatorcontrib>Sun, Yangyang</creatorcontrib><creatorcontrib>Su, Huimin</creatorcontrib><creatorcontrib>Xing, Wanjin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Theriogenology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Rina</au><au>Liu, Ruizhuo</au><au>Sun, Yangyang</au><au>Su, Huimin</au><au>Xing, Wanjin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO</atitle><jtitle>Theriogenology</jtitle><addtitle>Theriogenology</addtitle><date>2025-01-01</date><risdate>2025</risdate><volume>231</volume><spage>160</spage><epage>170</epage><pages>160-170</pages><issn>0093-691X</issn><issn>1879-3231</issn><eissn>1879-3231</eissn><abstract>In mammalian reproduction, testis-specific protein IZUMO1 and its receptor JUNO on the oocyte surface are essential for sperm-oocyte recognition, binding, and membrane fusion. However, these factors alone are insufficient to accomplish cytoplasmic membrane fusion. It is believed that other gametic proteins interact with them to facilitate sperm-oocyte interaction on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. In this study, Copper Transport Protein 2 (CTR2) has been identified on the head and mid-tail of rat spermatozoa as well as on the surface of oocytes. CTR2 directly interacts with both IZUMO1 and JUNO, colocalizing with IZUMO1 on the sperm head and with JUNO on the oocyte membrane. Treatment of the capacitated sperm and zona pellucida-free oocytes with anti-CTR2 antibody resulted in a significant decrease in fertilization rates in IVF experiments. These findings suggest that CTR2 plays an important role in mammalian fertilization by interacting with IZUMO1 and JUNO, providing new insights into the molecular mechanisms of mammalian sperm-oocyte adhesion and fusion.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39454481</pmid><doi>10.1016/j.theriogenology.2024.10.016</doi><tpages>11</tpages></addata></record> |
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subjects | adhesion animal reproduction Animals antibodies Cation Transport Proteins - genetics Cation Transport Proteins - metabolism cell membranes copper Copper Transport Proteins - metabolism CTR2 Female Fertilization - physiology head Immunoglobulins - metabolism IZUMO1 JUNO Male membrane fusion Membrane Proteins - genetics Membrane Proteins - metabolism oocytes Oocytes - metabolism Oocytes - physiology Protein-protein interaction Rats Sperm-egg fusion Sperm-Ovum Interactions - physiology spermatozoa Spermatozoa - metabolism Spermatozoa - physiology transport proteins |
title | Rat copper transport protein 2 (CTR2) is involved in fertilization through interaction with IZUMO1 and JUNO |
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