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Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in $Trypanosoma$ and human.

Charles Coutton 1, 2 Alexandra S. Vargas 1 Amir Amiri-yekta 1, 3, 4 Zine-Eddine Kherraf 1, 3 Selima Fourati Ben Mustapha 5 Pauline Le Tanno 1, 2 Clémentine Wambergue Legrand 1, 3 Thomas Karaouzène 1, 3, 6 Guillaume Martinez 1, 2 Serge Crouzy 7 Abbas Daneshipour 4 Seyedeh Hanieh Hosseini 8 Valerie Mitchell 9, 10 Lazhar Halouani 5 Marrakchi Ouafi 5 Mounir Makni 5 Habib Latrous 5 Mahmoud Kharouf 5 Jean-François Deleuze 11 Anne Boland 11 Sylviane Hennebicq 1, 12 Veronique Satre 1, 2 Pierre-Simon Jouk 13, 14 Nicolas Thierry-Mieg 6 Béatrice Conne 15 Denis Dacheux 16, 17 Nicolas Landrein 16 Alain Schmitt 18, 19 Laurence Stouvenel 18, 19 Patrick Lores 18, 19 Elma El Khouri 18, 19 Serge P. Bottari 1 Julien Faure 20, 21 Jean Philippe Wolf 19, 22 Karine Pernet-Gallay 21 Jessica Escoffier 1 Hamid Gourabi 4 Derrick R Robinson 16 Serge Nef 15 Emmanuel Dulioust 19, 22 Raoudha Zouari 5 Melanie Bonhivers 16 Aminata Toure 18, 19 Christophe Arnoult 1 Pierre F. Ray 1, 3, * 
* Corresponding author
6 TIMC-IMAG-BCM - Biologie Computationnelle et Mathématique
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
14 TIMC-IMAG-DyCTiM - Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies
TIMC-IMAG - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
Abstract : Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report men with primary infertility due to multiple morphological abnormalities of the sperm flagella with severe disorganization of the sperm axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-exome sequencing was performed on 78 patients allowing the identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n = 10), and CFAP44 (n = 6). CRISPR/Cas9 created homozygous CFAP43/44 male mice that were infertile and presented severe flagellar defects confirming the human genetic results. Immunoelectron and stimulated-emission-depletion microscopy performed on CFAP43 and CFAP44 orthologs in $Trypanosoma\ brucei$ evidenced that both proteins are located between the doublet microtubules 5 and 6 and the paraflagellar rod. Overall, we demonstrate that CFAP43 and CFAP44 have a similar structure with a unique axonemal localization and are necessary to produce functional flagella in species ranging from $Trypanosoma$ to human.
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https://hal.archives-ouvertes.fr/hal-01724640
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Submitted on : Tuesday, March 6, 2018 - 4:19:20 PM
Last modification on : Wednesday, March 23, 2022 - 3:51:24 PM

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Charles Coutton, Alexandra S. Vargas, Amir Amiri-yekta, Zine-Eddine Kherraf, Selima Fourati Ben Mustapha, et al.. Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in $Trypanosoma$ and human.. Nature Communications, Nature Publishing Group, 2018, 9, pp.686. ⟨10.1038/s41467-017-02792-7⟩. ⟨hal-01724640⟩

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