Spermiation: Insights from Studies on the Adjudin Model

Chen, Haiqi; Jiang, Yu; Mruk, Dolores D.; Cheng, C. Yan

doi:10.1007/978-3-030-77779-1_12

Cited by 4 publications

(3 citation statements)

References 48 publications

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“…It has been reported using genetic studies that at least 70 genes are involved in the process of spermiation/individualization, with a unique cooperation between Sertoli cells and the maturing elongated spermatids ( Hess and Vogl, 2015 ; Steinhauer, 2015 ). Several molecular pathways contribute to this process, including actin and microtubule dynamics, the ubiquitin-proteasome pathway components, apoptotic elimination of cytoplasmic contents, plasma membrane reorganization, and the formation of a disengagement complex ( O’Donnell and Stanton, 2018 ; Hess and Vogl, 2015 ; Steinhauer, 2015 ; Zhong and Belote, 2007 ; Chen et al, 2021 ). The microtubule cytoskeleton is important for spermiation/individualization ( Steinhauer, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice

Yap

Huang

et al. 2023

eLife

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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.

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Section: Discussionmentioning

confidence: 99%

DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice

Yap

Huang

et al. 2023

eLife

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show abstract

“…It has been reported using genetic studies that at least 70 genes are involved in the process of disengagement and individualization. Several molecular pathways contribute to this process, including actin and microtubule dynamics, the ubiquitin-proteasome pathway components, apoptotic elimination of cytoplasmic contents, plasma membrane reorganization, and the formation of a disengagement complex (65, 67, 71–73). The microtubule cytoskeleton is important for individualization (73).…”

Section: Discussionmentioning

confidence: 99%

“…Several molecular pathways contribute to this process, including actin and microtubule dynamics, the ubiquitin-proteasome pathway components, apoptotic elimination of cytoplasmic contents, plasma membrane reorganization, and the formation of a disengagement complex (65, 67, 71–73). The microtubule cytoskeleton is important for individualization (73). Complexes of microtubules and dynein and kinesin motors form the core of cilia and flagella (74).…”

Section: Discussionmentioning

confidence: 99%

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

Yap

Huang

et al. 2022

Preprint

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Axonemal dynein light intermediate polypeptide 1 (DNALI1) was originally cloned from Chlamydomonas reinhardtii in an effort to find motor proteins essential for flagellar motility. Here we report that DNALI1 is a binding partner of parkin co-regulated gene 1 (PACRG), which forms a complex with meiosis expressed gene 1 (MEIG1) in the manchette, a transient and unique structure only present in the elongating spermatids and required for normal spermiogenesis of the male germ cell differentiation process. DNALI1 recruits the PACRG protein in transfected CHO cells, and also stabilizes PACRG in bacteria and transfected mammalian cells. The untagged DNALI1 could also be co-purified with His-tagged PACRG in the gel filtration assay. Immunofluorescence staining on isolated male germ cells revealed that DNALI1 was present in the manchette of elongating spermatids, and colocalized with PACRG in this structure. In Pacrg mutant mice, localization of DNALI1 in the manchette was not changed, suggesting that DNALI1 and PACRG form a complex in the manchette, with DNALI1 being an upstream molecule. Mice deficiency in DNALI1 specifically in male germ cells showed dramatically reduced sperm numbers and were infertile. In addition, majority of the sperm exhibited abnormal morphology including misshapen heads, bent tails and enlarged midpiece, discontinuous accessory structure, and loss of sperm individualization, emphasizing the importance of DNALI1 in sperm development. Examination of testis histology revealed impaired spermiogenesis in the conditional Dnali1 knockout mice. Electron microscopy revealed disrupted ultrastructure in sperm of the Dnali1 mutant mice. Testicular levels of MEIG1, PACRG and SPAG16L proteins were not changed in the Dnali1 mutant mice. However, MEIG1 and SPAG16L were no longer present in the manchette in the absence of DNALI1. These findings demonstrate that DNALI1 is involved in the connection of the MEIG1/PACRG complex to carry cargo proteins along the manchette microtubules for sperm flagella formation. Given that Dnali1 mutant mice showed impaired sperm individualization that was not observed in the MEIG1 nor PACRG-deficient mice, DNALI1 might fulfill other functions beyond its role associated with the MEIG1/PACRG complex. Thus, DNALI1 plays multiple roles in sperm cell differentiation and function.Summary statementAxonemal dynein light intermediate polypeptide 1 (DNALI1) is required for sperm formation and male fertility. It associates with the MEIG1/PACRG complex in the manchette and is involved in a cargo transport system. In addition, it might be related to IFT and sperm individualization.

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Identification of proline-rich protein 11 as a major regulator in mouse spermatogonia maintenance via an increase in BMI1 protein stability

Xue

Huang

et al. 2022

Mol Biol Rep

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Spermiation: Insights from Studies on the Adjudin Model

Cited by 4 publications

References 48 publications

DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice

DNALI1 interacts with the MEIG1/PACRG complex within the manchette and is required for proper sperm flagellum assembly in mice

MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis

Identification of proline-rich protein 11 as a major regulator in mouse spermatogonia maintenance via an increase in BMI1 protein stability

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