Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads
Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the tes...
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| description | Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility. |
| doi_str_mv | 10.1371/journal.pgen.1011337 |
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The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1011337</identifier><identifier>PMID: 38935810</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acrosome - metabolism ; Amino acids ; Animals ; Binding proteins ; Biology and Life Sciences ; Cell division ; Family ; Fertility ; Fertility - genetics ; Genetic aspects ; Golgi apparatus ; Golgi Apparatus - metabolism ; Health aspects ; Infertility ; Infertility, Male - genetics ; Infertility, Male - metabolism ; Male ; Males ; Medicine and Health Sciences ; Membrane proteins ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membrane trafficking ; Mice ; Mice, Knockout ; Morphogenesis ; Morphogenesis - genetics ; Morphology ; Phylogenetics ; Protein structure ; Protein transport ; Proteins ; rab2 GTP-Binding Protein - genetics ; rab2 GTP-Binding Protein - metabolism ; Sperm ; Sperm Head - metabolism ; Spermatogenesis ; Spermatozoa ; Spermatozoa - metabolism ; Testes ; Testis - growth & development ; Testis - metabolism ; Vacuoles</subject><ispartof>PLoS genetics, 2024-06, Vol.20 (6), p.e1011337</ispartof><rights>Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Wang et al 2024 Wang et al</rights><rights>2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c606t-d9aac6e440b5a6196c093d782ac46d0252763c656ecfb54b40c8938b33f358553</cites><orcidid>0009-0000-5176-7170 ; 0000-0003-0104-1974 ; 0000-0001-9859-6217 ; 0000-0003-4758-5803 ; 0000-0003-3927-3076</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236154/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236154/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38935810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Wang, Haoting</creatorcontrib><creatorcontrib>Iida-Norita, Rie</creatorcontrib><creatorcontrib>Mashiko, Daisuke</creatorcontrib><creatorcontrib>Pham, Anh Hoang</creatorcontrib><creatorcontrib>Miyata, Haruhiko</creatorcontrib><creatorcontrib>Ikawa, Masahito</creatorcontrib><title>Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.</description><subject>Acrosome - metabolism</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Binding proteins</subject><subject>Biology and Life Sciences</subject><subject>Cell division</subject><subject>Family</subject><subject>Fertility</subject><subject>Fertility - genetics</subject><subject>Genetic aspects</subject><subject>Golgi apparatus</subject><subject>Golgi Apparatus - metabolism</subject><subject>Health aspects</subject><subject>Infertility</subject><subject>Infertility, Male - genetics</subject><subject>Infertility, Male - metabolism</subject><subject>Male</subject><subject>Males</subject><subject>Medicine and Health Sciences</subject><subject>Membrane proteins</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane trafficking</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Morphogenesis</subject><subject>Morphogenesis - 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genetics</topic><topic>rab2 GTP-Binding Protein - metabolism</topic><topic>Sperm</topic><topic>Sperm Head - metabolism</topic><topic>Spermatogenesis</topic><topic>Spermatozoa</topic><topic>Spermatozoa - metabolism</topic><topic>Testes</topic><topic>Testis - growth & development</topic><topic>Testis - metabolism</topic><topic>Vacuoles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Haoting</creatorcontrib><creatorcontrib>Iida-Norita, Rie</creatorcontrib><creatorcontrib>Mashiko, Daisuke</creatorcontrib><creatorcontrib>Pham, Anh Hoang</creatorcontrib><creatorcontrib>Miyata, Haruhiko</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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Haoting</au><au>Iida-Norita, Rie</au><au>Mashiko, Daisuke</au><au>Pham, Anh Hoang</au><au>Miyata, Haruhiko</au><au>Ikawa, Masahito</au><au>Barsh, Gregory S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2024-06-27</date><risdate>2024</risdate><volume>20</volume><issue>6</issue><spage>e1011337</spage><pages>e1011337-</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38935810</pmid><doi>10.1371/journal.pgen.1011337</doi><tpages>e1011337</tpages><orcidid>https://orcid.org/0009-0000-5176-7170</orcidid><orcidid>https://orcid.org/0000-0003-0104-1974</orcidid><orcidid>https://orcid.org/0000-0001-9859-6217</orcidid><orcidid>https://orcid.org/0000-0003-4758-5803</orcidid><orcidid>https://orcid.org/0000-0003-3927-3076</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PLoS genetics, 2024-06, Vol.20 (6), p.e1011337 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acrosome - metabolism Amino acids Animals Binding proteins Biology and Life Sciences Cell division Family Fertility Fertility - genetics Genetic aspects Golgi apparatus Golgi Apparatus - metabolism Health aspects Infertility Infertility, Male - genetics Infertility, Male - metabolism Male Males Medicine and Health Sciences Membrane proteins Membrane Proteins - genetics Membrane Proteins - metabolism Membrane trafficking Mice Mice, Knockout Morphogenesis Morphogenesis - genetics Morphology Phylogenetics Protein structure Protein transport Proteins rab2 GTP-Binding Protein - genetics rab2 GTP-Binding Protein - metabolism Sperm Sperm Head - metabolism Spermatogenesis Spermatozoa Spermatozoa - metabolism Testes Testis - growth & development Testis - metabolism Vacuoles |
| title | Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T13%3A03%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Golgi%20associated%20RAB2%20interactor%20protein%20family%20contributes%20to%20murine%20male%20fertility%20to%20various%20extents%20by%20assuring%20correct%20morphogenesis%20of%20sperm%20heads&rft.jtitle=PLoS%20genetics&rft.au=Wang,%20Haoting&rft.date=2024-06-27&rft.volume=20&rft.issue=6&rft.spage=e1011337&rft.pages=e1011337-&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1011337&rft_dat=%3Cgale_plos_%3EA800672029%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3086942961&rft_id=info:pmid/38935810&rft_galeid=A800672029&rft_doaj_id=oai_doaj_org_article_7d3232befcf647919e47c17976cc0bd9&rfr_iscdi=true |