Tetraspanin Cd9b plays a role in fertility in zebrafish

Greaves, Sarah; Marsay, Katherine S.; Monk, Peter N.; Roehl, Henry; Partridge, Lynda J.

doi:10.1371/journal.pone.0277274

Cited by 6 publications

(1 citation statement)

References 36 publications

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“…Of direct relevance to these questions is an independent study, submitted back to back with the original preprint of the present manuscript, which provides experimental data for the existence of a trimeric IZUMO1/SPACA6/TMEM81 complex in zebrafish and suggests that this interacts with egg Bouncer (Deneke et al, 2023) . Considering that the mammalian orthologue of Bouncer is expressed on sperm instead of the egg (Fujihara et al, 2021) and that role of CD9 in egg-sperm fusion is much more important in mammals than in fish (Greaves et al, 2022) , the combination of our studies raises the intriguing possibility that, during the course of evolution, CD9 may have substituted Bouncer as a binding partner of the IZUMO1/SPACA6/TMEM81 complex.…”

Section: Discussionmentioning

confidence: 91%

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

Elofsson

Han

Bianchi

et al. 2023

Preprint

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Fertilization is a crucial event in sexual reproduction culminating in the fusion of the haploid sperm and egg to form a new diploid organism. In mammals, egg receptor JUNO and sperm IZUMO1 directly interact to mediate adhesion between gamete membranes; however, their role in fusion remains enigmatic. Here, we used AlphaFold to predict the structure of other extracellular proteins that are essential for fertilization and determine if they could form a fusogenic complex. We first identified TMEM81, whose gene is expressed by mouse spermatids, as a protein that has structural homologies with both IZUMO1 and another essential sperm ligand, SPACA6. Using a set of proteins known to be important for fertilization, we systematically searched for predicted direct binary interactions using an unguided approach. We identified a tetrameric complex of two sperm (IZUMO1 and SPACA6) and two egg (JUNO and CD9) proteins, and further modeling using this core complex identified TMEM81 as an additional component. We show that the complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-linked glycans that were not considered during prediction with AlphaFold-Multimer. Our model suggests that these proteins could organize to form a synapse-like complex between the sperm and egg membrane at the point of fertilization. Finally, the structural modeling approach described here could be more generally useful to gain structural insights into highly transient protein complexes that are difficult to detect experimentally.

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Section: Discussionmentioning

confidence: 91%

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

Elofsson

Han

Bianchi

et al. 2023

Preprint

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Testis transcriptomic analyses reveal the effects of an algae feed on sperm quality in Senegalese sole during the breeding season

Félix,

Raposo de Magalhães,

Marrero-Alemán

et al. 2025

Aquaculture

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Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

Elofsson,

Han,

Bianchi

et al. 2024

eLife

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Fertilization is a crucial event in sexual reproduction culminating in the fusion of the haploid sperm and egg to form a new diploid organism. In mammals, egg receptor JUNO and sperm IZUMO1 directly interact to mediate adhesion between gamete membranes; however, their role in fusion remains enigmatic. Here, we used AlphaFold to predict the structure of other extracellular proteins that are essential for fertilization to determine if they could form a complex that may mediate fusion. We first identified TMEM81, whose gene is expressed by mouse and human spermatids, as a protein that has structural homologies with both IZUMO1 and another sperm molecule essential for gamete fusion, SPACA6. Using a set of proteins known to be important for fertilization and TMEM81, we then systematically searched for predicted direct binary interactions using an unguided approach and identified a pentameric complex of three sperm (IZUMO1, SPACA6 and TMEM81) and two egg (JUNO and CD9) proteins. We show that this complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-linked glycans that were not considered during prediction with AlphaFold-Multimer. Our model suggests that these proteins could organize to form a synapse-like complex between the sperm and egg membrane at the point of fertilization. Finally, the structural modeling approach described here could be more generally useful to gain structural insights into highly transient protein complexes that are difficult to detect experimentally.

show abstract

Tetraspanin Cd9b plays a role in fertility in zebrafish

Cited by 6 publications

References 36 publications

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

Testis transcriptomic analyses reveal the effects of an algae feed on sperm quality in Senegalese sole during the breeding season

Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse

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