DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice
The manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis. Previous work indicated that the MEIG1/PACRG complex locates in the manchette and is involved in the transport of cargos, such as SPAG1...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79620 |
| _version_ | 1797826610603229184 |
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| author | Yi Tian Yap Wei Li Qian Huang Qi Zhou David Zhang Yi Sheng Ljljiana Mladenovic-Lucas Siu-Pok Yee Kyle E Orwig James G Granneman David C Williams Jr Rex A Hess Aminata Toure Zhibing Zhang |
| author_facet | Yi Tian Yap Wei Li Qian Huang Qi Zhou David Zhang Yi Sheng Ljljiana Mladenovic-Lucas Siu-Pok Yee Kyle E Orwig James G Granneman David C Williams Jr Rex A Hess Aminata Toure Zhibing Zhang |
| author_sort | Yi Tian Yap |
| collection | DOAJ |
| description | The manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis. Previous work indicated that the MEIG1/PACRG complex locates in the manchette and is involved in the transport of cargos, such as SPAG16L, to build the sperm flagellum. Here, using co-immunoprecipitation and pull-down approaches in various cell systems, we established that DNALI1, an axonemal component originally cloned from Chlamydomonas reinhardtii, recruits and stabilizes PACRG and we confirm in vivo, the co-localization of DNALI1 and PACRG in the manchette by immunofluorescence of elongating murine spermatids. We next generated mice with a specific deficiency of DNALI1 in male germ cells, and observed a dramatic reduction of the sperm cells, which results in male infertility. In addition, we observed that the majority of the sperm cells exhibited abnormal morphology including misshapen heads, bent tails, enlarged midpiece, discontinuous accessory structure, emphasizing the importance of DNALI1 in sperm differentiation. Examination of testis histology confirmed impaired spermiogenesis in the mutant mice. Importantly, while testicular levels of MEIG1, PACRG, and SPAG16L proteins were unchanged in the Dnali1 mutant mice, their localization within the manchette was greatly affected, indicating that DNALI1 is required for the formation of the MEIG1/PACRG complex within the manchette. Interestingly, in contrast to MEIG1 and PACRG-deficient mice, the DNALI1-deficient mice also showed impaired sperm spermiation/individualization, suggesting additional functions beyond its involvement in the manchette structure. Overall, our work identifies DNALI1 as a protein required for sperm development. |
| first_indexed | 2024-04-09T12:35:10Z |
| format | Article |
| id | doaj.art-38f61c35e05a4db99d95d69fa557bcfc |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T12:35:10Z |
| publishDate | 2023-04-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-38f61c35e05a4db99d95d69fa557bcfc2023-05-15T13:07:36ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.79620DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in miceYi Tian Yap0https://orcid.org/0000-0001-6448-2748Wei Li1Qian Huang2https://orcid.org/0000-0001-6836-5135Qi Zhou3David Zhang4Yi Sheng5Ljljiana Mladenovic-Lucas6Siu-Pok Yee7https://orcid.org/0000-0002-2427-401XKyle E Orwig8James G Granneman9https://orcid.org/0000-0001-7013-6630David C Williams Jr10https://orcid.org/0000-0002-6536-4038Rex A Hess11https://orcid.org/0000-0003-2649-3563Aminata Toure12Zhibing Zhang13https://orcid.org/0000-0002-8615-4478Department of Physiology, Wayne State University School of Medicine, Detroit, United StatesDepartment of Physiology, Wayne State University School of Medicine, Detroit, United StatesDepartment of Physiology, Wayne State University School of Medicine, Detroit, United States; Department of Occupational and Environmental Medicine, School of Public Health, Wuhan University of Science and Technology, Wuhan, ChinaDepartment of Physiology, Wayne State University School of Medicine, Detroit, United States; Department of Occupational and Environmental Medicine, School of Public Health, Wuhan University of Science and Technology, Wuhan, ChinaCollege of William and Mary, Williamsburg, United StatesMolecular Genetics and Developmental Biology Graduate Program, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, United StatesCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, United StatesDepartment of Cell Biology, University of Connecticut Health Center, Farmington, United StatesMolecular Genetics and Developmental Biology Graduate Program, Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, United StatesCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, United StatesDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, United StatesDepartment of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, United StatesUniversity Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team Physiology and Pathophysiology of Sperm cells, Institute for Advanced Biosciences, Grenoble, FranceDepartment of Physiology, Wayne State University School of Medicine, Detroit, United States; Department of Obstetrics & Gynecology, Wayne State University, Detroit, United StatesThe manchette is a transient and unique structure present in elongating spermatids and required for proper differentiation of the germ cells during spermatogenesis. Previous work indicated that the MEIG1/PACRG complex locates in the manchette and is involved in the transport of cargos, such as SPAG16L, to build the sperm flagellum. Here, using co-immunoprecipitation and pull-down approaches in various cell systems, we established that DNALI1, an axonemal component originally cloned from Chlamydomonas reinhardtii, recruits and stabilizes PACRG and we confirm in vivo, the co-localization of DNALI1 and PACRG in the manchette by immunofluorescence of elongating murine spermatids. We next generated mice with a specific deficiency of DNALI1 in male germ cells, and observed a dramatic reduction of the sperm cells, which results in male infertility. In addition, we observed that the majority of the sperm cells exhibited abnormal morphology including misshapen heads, bent tails, enlarged midpiece, discontinuous accessory structure, emphasizing the importance of DNALI1 in sperm differentiation. Examination of testis histology confirmed impaired spermiogenesis in the mutant mice. Importantly, while testicular levels of MEIG1, PACRG, and SPAG16L proteins were unchanged in the Dnali1 mutant mice, their localization within the manchette was greatly affected, indicating that DNALI1 is required for the formation of the MEIG1/PACRG complex within the manchette. Interestingly, in contrast to MEIG1 and PACRG-deficient mice, the DNALI1-deficient mice also showed impaired sperm spermiation/individualization, suggesting additional functions beyond its involvement in the manchette structure. Overall, our work identifies DNALI1 as a protein required for sperm development.https://elifesciences.org/articles/79620DNALI1manchettecargo transportspermatogenesis |
| spellingShingle | Yi Tian Yap Wei Li Qian Huang Qi Zhou David Zhang Yi Sheng Ljljiana Mladenovic-Lucas Siu-Pok Yee Kyle E Orwig James G Granneman David C Williams Jr Rex A Hess Aminata Toure Zhibing Zhang DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice eLife DNALI1 manchette cargo transport spermatogenesis |
| title | DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice |
| title_full | DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice |
| title_fullStr | DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice |
| title_full_unstemmed | DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice |
| title_short | DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice |
| title_sort | dnali1 interacts with the meig1 pacrg complex within the manchette and is required for proper sperm flagellum assembly in mice |
| topic | DNALI1 manchette cargo transport spermatogenesis |
| url | https://elifesciences.org/articles/79620 |
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