Androglobin, a chimeric mammalian globin, is required for male fertility
Spermatogenesis is a highly specialised differentiation process driven by a dynamic gene expression program and ending with the production of mature spermatozoa. Whereas hundreds of genes are known to be essential for male germline proliferation and differentiation, the contribution of several genes remains uncharacterized. The predominant expression of the latest globin family member, androglobin (Adgb), in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape and ultrastructural defects in microtubule and mitochondrial organisation. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifid or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates, and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, absence of Adgb leads to mislocalisation of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin (CaM)-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that Adgb is required for sperm head shaping via the manchette and proper flagellum formation.
RNA-sequencing data have been submitted to ENA with accession number PRJEB46499 and is also available as supplemental dataset 1 (excel table).All data generated or analysed during this study are included in the manuscript and supporting files. Source data files are provided for Figures 1, 2, 4B, 4C, 4D, 4E, 6A, 6B, 6C, 6D, 6E, 6F, Fig. 1-fig. suppl. 1, Fig. 4-fig. suppl. 1A, B, C, D, E, F, G, Fig. 4-fig. suppl. 2A, B, C, Fig. 4-fig. suppl. 3A, B, C, D, E, Fig. 4-fig. suppl. 5, Fig. 4-fig. suppl. 6B, Fig. 6-fig. suppl. 1A, Fig. 6-fig. suppl. 4, Fig. 6-fig. suppl. 5D, E.
Article and author information
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_173000)
- David Hoogewijs
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_207460)
- David Hoogewijs
Deutsche Forschungsgemeinschaft (HO 5837/1-1)
- David Hoogewijs
Deutsche Forschungsgemeinschaft (HA 2103/9-1)
- Thomas Hankeln
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experimental procedures and animal maintenance followed Swiss federal guidelines and the study was revised and approved by the "Service de la sécurité alimentaire et des affaires vétérinaires" (SAAV) of the canton of Fribourg, Switzerland (license number 2017_16_FR).
- T Rajendra Kumar, University of Colorado, United States
- Received: July 21, 2021
- Preprint posted: September 18, 2021 (view preprint)
- Accepted: June 13, 2022
- Accepted Manuscript published: June 14, 2022 (version 1)
- Version of Record published: July 1, 2022 (version 2)
© 2022, Keppner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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