SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice
Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because s...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2021-08, Vol.118 (35), p.1-9 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9 |
|---|---|
| container_issue | 35 |
| container_start_page | 1 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 118 |
| creator | Miyata, Haruhiko Oura, Seiya Morohoshi, Akane Shimada, Keisuke Mashiko, Daisuke Oyama, Yuki Kaneda, Yuki Matsumura, Takafumi Abbasi, Ferheen Ikawa, Masahito |
| description | Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors. Here, by screening the calcineurin-interacting PxIxIT consensus motif in silico and analyzing the function of candidate proteins through the generation of gene-modified mice, we discovered that SPATA33 interacts with sperm calcineurin via a PQIIIT sequence. Spata33 knockout mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility, which phenocopies Ppp3cc and Ppp3r2 knockout mice. Further analysis reveals that sperm calcineurin disappears from the mitochondria in the Spata33 knockout testis. In addition, immunoprecipitation analysis indicates that sperm calcineurin interacts with not only SPATA33 but also the mitochondrial protein VDAC2. These results indicate that SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility. |
| doi_str_mv | 10.1073/pnas.2106673118 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8536318</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>27075320</jstor_id><sourcerecordid>27075320</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4248-a79837e3a17ed13adaccb682062e9fc5627e74a8cd9dc813074a61033833408b3</originalsourceid><addsrcrecordid>eNpdkd1rFDEUxYModq0--6QM-OLLtDe5mSTzIizFLyhYaPU1ZDPZbpaZZE0yQv3rzbJ1bX06XO7vHs7lEPKawhkFiee7YPIZoyCERErVE7Kg0NNW8B6ekgUAk63ijJ-QFzlvAaDvFDwnJ8g5F12nFuTH9dXyZonYjNGa0f92ualqfXBz8qEpsSkb10y-RLuJYUjeNCYMTXK382hKpfPOpamZYvGjL3dNvZm8dS_Js7UZs3t1r6fk-6ePNxdf2stvn79eLC9bW1Op1sheoXRoqHQDRTMYa1dCMRDM9WvbCSad5EbZoR-sogh1EBQQFSIHtcJT8uHgu5tXkxusCyWZUe-Sn0y609F4_XgT_Ebfxl9adSiQqmrw_t4gxZ-zy0VPPls3jia4OGfNOiGAC0a7ir77D93GOYX63p7qOWW9gEqdHyibYs7JrY9hKOh9Z3rfmf7XWb14-_CHI_-3pAq8OQDbXGI67pkE2SED_AMDcZwq</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2569412960</pqid></control><display><type>article</type><title>SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Miyata, Haruhiko ; Oura, Seiya ; Morohoshi, Akane ; Shimada, Keisuke ; Mashiko, Daisuke ; Oyama, Yuki ; Kaneda, Yuki ; Matsumura, Takafumi ; Abbasi, Ferheen ; Ikawa, Masahito</creator><creatorcontrib>Miyata, Haruhiko ; Oura, Seiya ; Morohoshi, Akane ; Shimada, Keisuke ; Mashiko, Daisuke ; Oyama, Yuki ; Kaneda, Yuki ; Matsumura, Takafumi ; Abbasi, Ferheen ; Ikawa, Masahito</creatorcontrib><description>Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors. Here, by screening the calcineurin-interacting PxIxIT consensus motif in silico and analyzing the function of candidate proteins through the generation of gene-modified mice, we discovered that SPATA33 interacts with sperm calcineurin via a PQIIIT sequence. Spata33 knockout mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility, which phenocopies Ppp3cc and Ppp3r2 knockout mice. Further analysis reveals that sperm calcineurin disappears from the mitochondria in the Spata33 knockout testis. In addition, immunoprecipitation analysis indicates that sperm calcineurin interacts with not only SPATA33 but also the mitochondrial protein VDAC2. These results indicate that SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2106673118</identifier><identifier>PMID: 34446558</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological activity ; Biological Sciences ; Calcineurin ; Calcineurin - genetics ; Calcineurin - metabolism ; Calcium ; Contraceptives ; Female ; Fertility ; Immune response ; Immunoprecipitation ; Intercellular Signaling Peptides and Proteins - physiology ; Male ; Males ; Mice ; Mice, Knockout ; Mitochondria ; Mitochondria - metabolism ; Motility ; Proteins ; Rodents ; Sperm ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Testes ; Testis - physiology ; Voltage-Dependent Anion Channel 2 - genetics ; Voltage-Dependent Anion Channel 2 - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-08, Vol.118 (35), p.1-9</ispartof><rights>Copyright National Academy of Sciences Aug 31, 2021</rights><rights>2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4248-a79837e3a17ed13adaccb682062e9fc5627e74a8cd9dc813074a61033833408b3</citedby><cites>FETCH-LOGICAL-c4248-a79837e3a17ed13adaccb682062e9fc5627e74a8cd9dc813074a61033833408b3</cites><orcidid>0000-0003-4758-5803 ; 0000-0001-5572-8734 ; 0000-0003-3739-7163 ; 0000-0002-7606-732X ; 0000-0001-9859-6217</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27075320$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27075320$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34446558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyata, Haruhiko</creatorcontrib><creatorcontrib>Oura, Seiya</creatorcontrib><creatorcontrib>Morohoshi, Akane</creatorcontrib><creatorcontrib>Shimada, Keisuke</creatorcontrib><creatorcontrib>Mashiko, Daisuke</creatorcontrib><creatorcontrib>Oyama, Yuki</creatorcontrib><creatorcontrib>Kaneda, Yuki</creatorcontrib><creatorcontrib>Matsumura, Takafumi</creatorcontrib><creatorcontrib>Abbasi, Ferheen</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><title>SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors. Here, by screening the calcineurin-interacting PxIxIT consensus motif in silico and analyzing the function of candidate proteins through the generation of gene-modified mice, we discovered that SPATA33 interacts with sperm calcineurin via a PQIIIT sequence. Spata33 knockout mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility, which phenocopies Ppp3cc and Ppp3r2 knockout mice. Further analysis reveals that sperm calcineurin disappears from the mitochondria in the Spata33 knockout testis. In addition, immunoprecipitation analysis indicates that sperm calcineurin interacts with not only SPATA33 but also the mitochondrial protein VDAC2. These results indicate that SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility.</description><subject>Animals</subject><subject>Biological activity</subject><subject>Biological Sciences</subject><subject>Calcineurin</subject><subject>Calcineurin - genetics</subject><subject>Calcineurin - metabolism</subject><subject>Calcium</subject><subject>Contraceptives</subject><subject>Female</subject><subject>Fertility</subject><subject>Immune response</subject><subject>Immunoprecipitation</subject><subject>Intercellular Signaling Peptides and Proteins - physiology</subject><subject>Male</subject><subject>Males</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Motility</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Sperm</subject><subject>Sperm Motility</subject><subject>Spermatogenesis</subject><subject>Spermatozoa</subject><subject>Testes</subject><subject>Testis - physiology</subject><subject>Voltage-Dependent Anion Channel 2 - genetics</subject><subject>Voltage-Dependent Anion Channel 2 - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd1rFDEUxYModq0--6QM-OLLtDe5mSTzIizFLyhYaPU1ZDPZbpaZZE0yQv3rzbJ1bX06XO7vHs7lEPKawhkFiee7YPIZoyCERErVE7Kg0NNW8B6ekgUAk63ijJ-QFzlvAaDvFDwnJ8g5F12nFuTH9dXyZonYjNGa0f92ualqfXBz8qEpsSkb10y-RLuJYUjeNCYMTXK382hKpfPOpamZYvGjL3dNvZm8dS_Js7UZs3t1r6fk-6ePNxdf2stvn79eLC9bW1Op1sheoXRoqHQDRTMYa1dCMRDM9WvbCSad5EbZoR-sogh1EBQQFSIHtcJT8uHgu5tXkxusCyWZUe-Sn0y609F4_XgT_Ebfxl9adSiQqmrw_t4gxZ-zy0VPPls3jia4OGfNOiGAC0a7ir77D93GOYX63p7qOWW9gEqdHyibYs7JrY9hKOh9Z3rfmf7XWb14-_CHI_-3pAq8OQDbXGI67pkE2SED_AMDcZwq</recordid><startdate>20210831</startdate><enddate>20210831</enddate><creator>Miyata, Haruhiko</creator><creator>Oura, Seiya</creator><creator>Morohoshi, Akane</creator><creator>Shimada, Keisuke</creator><creator>Mashiko, Daisuke</creator><creator>Oyama, Yuki</creator><creator>Kaneda, Yuki</creator><creator>Matsumura, Takafumi</creator><creator>Abbasi, Ferheen</creator><creator>Ikawa, Masahito</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4758-5803</orcidid><orcidid>https://orcid.org/0000-0001-5572-8734</orcidid><orcidid>https://orcid.org/0000-0003-3739-7163</orcidid><orcidid>https://orcid.org/0000-0002-7606-732X</orcidid><orcidid>https://orcid.org/0000-0001-9859-6217</orcidid></search><sort><creationdate>20210831</creationdate><title>SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice</title><author>Miyata, Haruhiko ; Oura, Seiya ; Morohoshi, Akane ; Shimada, Keisuke ; Mashiko, Daisuke ; Oyama, Yuki ; Kaneda, Yuki ; Matsumura, Takafumi ; Abbasi, Ferheen ; Ikawa, Masahito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4248-a79837e3a17ed13adaccb682062e9fc5627e74a8cd9dc813074a61033833408b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Biological activity</topic><topic>Biological Sciences</topic><topic>Calcineurin</topic><topic>Calcineurin - genetics</topic><topic>Calcineurin - metabolism</topic><topic>Calcium</topic><topic>Contraceptives</topic><topic>Female</topic><topic>Fertility</topic><topic>Immune response</topic><topic>Immunoprecipitation</topic><topic>Intercellular Signaling Peptides and Proteins - physiology</topic><topic>Male</topic><topic>Males</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Motility</topic><topic>Proteins</topic><topic>Rodents</topic><topic>Sperm</topic><topic>Sperm Motility</topic><topic>Spermatogenesis</topic><topic>Spermatozoa</topic><topic>Testes</topic><topic>Testis - physiology</topic><topic>Voltage-Dependent Anion Channel 2 - genetics</topic><topic>Voltage-Dependent Anion Channel 2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyata, Haruhiko</creatorcontrib><creatorcontrib>Oura, Seiya</creatorcontrib><creatorcontrib>Morohoshi, Akane</creatorcontrib><creatorcontrib>Shimada, Keisuke</creatorcontrib><creatorcontrib>Mashiko, Daisuke</creatorcontrib><creatorcontrib>Oyama, Yuki</creatorcontrib><creatorcontrib>Kaneda, Yuki</creatorcontrib><creatorcontrib>Matsumura, Takafumi</creatorcontrib><creatorcontrib>Abbasi, Ferheen</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyata, Haruhiko</au><au>Oura, Seiya</au><au>Morohoshi, Akane</au><au>Shimada, Keisuke</au><au>Mashiko, Daisuke</au><au>Oyama, Yuki</au><au>Kaneda, Yuki</au><au>Matsumura, Takafumi</au><au>Abbasi, Ferheen</au><au>Ikawa, Masahito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2021-08-31</date><risdate>2021</risdate><volume>118</volume><issue>35</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Calcineurin is a calcium-dependent phosphatase that plays roles in a variety of biological processes including immune responses. In spermatozoa, there is a testis-enriched calcineurin composed of PPP3CC and PPP3R2 (sperm calcineurin) that is essential for sperm motility and male fertility. Because sperm calcineurin has been proposed as a target for reversible male contraceptives, identifying proteins that interact with sperm calcineurin widens the choice for developing specific inhibitors. Here, by screening the calcineurin-interacting PxIxIT consensus motif in silico and analyzing the function of candidate proteins through the generation of gene-modified mice, we discovered that SPATA33 interacts with sperm calcineurin via a PQIIIT sequence. Spata33 knockout mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility, which phenocopies Ppp3cc and Ppp3r2 knockout mice. Further analysis reveals that sperm calcineurin disappears from the mitochondria in the Spata33 knockout testis. In addition, immunoprecipitation analysis indicates that sperm calcineurin interacts with not only SPATA33 but also the mitochondrial protein VDAC2. These results indicate that SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>34446558</pmid><doi>10.1073/pnas.2106673118</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4758-5803</orcidid><orcidid>https://orcid.org/0000-0001-5572-8734</orcidid><orcidid>https://orcid.org/0000-0003-3739-7163</orcidid><orcidid>https://orcid.org/0000-0002-7606-732X</orcidid><orcidid>https://orcid.org/0000-0001-9859-6217</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2021-08, Vol.118 (35), p.1-9 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8536318 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Biological activity Biological Sciences Calcineurin Calcineurin - genetics Calcineurin - metabolism Calcium Contraceptives Female Fertility Immune response Immunoprecipitation Intercellular Signaling Peptides and Proteins - physiology Male Males Mice Mice, Knockout Mitochondria Mitochondria - metabolism Motility Proteins Rodents Sperm Sperm Motility Spermatogenesis Spermatozoa Testes Testis - physiology Voltage-Dependent Anion Channel 2 - genetics Voltage-Dependent Anion Channel 2 - metabolism |
| title | SPATA33 localizes calcineurin to the mitochondria and regulates sperm motility in mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T14%3A49%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SPATA33%20localizes%20calcineurin%20to%20the%20mitochondria%20and%20regulates%20sperm%20motility%20in%20mice&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Miyata,%20Haruhiko&rft.date=2021-08-31&rft.volume=118&rft.issue=35&rft.spage=1&rft.epage=9&rft.pages=1-9&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2106673118&rft_dat=%3Cjstor_pubme%3E27075320%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2569412960&rft_id=info:pmid/34446558&rft_jstor_id=27075320&rfr_iscdi=true |