Androglobin, a chimeric mammalian globin, is required for male fertility

Author:

Keppner Anna1,Correia Miguel1,Santambrogio Sara2,Koay Teng Wei1,Maric Darko1,Osterhof Carina3ORCID,Winter Denise V4,Clerc Angèle1,Stumpe Michael5ORCID,Chalmel Frédéric6,Dewilde Sylvia7,Odermatt Alex4,Kressler Dieter5ORCID,Hankeln Thomas3,Wenger Roland H2,Hoogewijs David1ORCID

Affiliation:

1. Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg

2. Institute of Physiology, University of Zurich

3. Institute for Organismic and Molecular Evolutionary Biology, University of Mainz

4. Department of Pharmaceutical Sciences, University of Basel

5. Department of Biology, University of Fribourg

6. University of Rennes, Inserm, UMR_S 1085

7. Department of Biomedical Sciences, University of Antwerp

Abstract

Spermatogenesis is a highly specialized 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 organization. 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, the absence of Adgb leads to mislocalization 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-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.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Deutsche Forschungsgemeinschaft

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference70 articles.

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3. The sperm centrioles;Avidor-Reiss;Molecular and Cellular Endocrinology,2020

4. Calmodulin signaling via the IQ motif;Bähler;FEBS Letters,2002

5. Exploring three different expression systems for recombinant expression of globins: Escherichia coli, Pichia pastoris and Spodoptera frugiperda;Bracke;Analytical Biochemistry,2018

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