Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in $Trypanosoma$ and human. - BCM : Biologie Computationnelle et Mathématique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2018

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

1 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 Laboratoire de Génétique Chromosomique [CHU de Grenoble]
3 CHU de Grenoble, UM GI-DPI, 38000, Grenoble, France.
4 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACER, Tehran, 16635-148, Iran.
5 Polyclinique les Jasmins [Tunis]
6 TIMC-IMAG-BCM - Biologie Computationnelle et Mathématique
7 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
8 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 16635-148, Iran.
9 Department of Reproductive Biology and Spermiology-CECOS Lille, University Medical Center, Lille, 59037, France.
10 GQG - Gamétogenèse et Qualité du Gamète - ULR 4308
11 IG - Institut de Génomique d'Evry
12 CHU de Grenoble, UF de Biologie de la procréation, 38000, Grenoble, France.
13 CHU de Grenoble, UF de Génétique Médicale, 38000, Grenoble, France.
14 TIMC-IMAG-DyCTiM2 - Dynamiques Cellulaire et Tissulaire - Interdisciplinarité, Modélisation & Microscopie
15 Department of Genetic Medicine and Development [Geneva]
16 MFP - Microbiologie Fondamentale et Pathogénicité
17 Bordeaux INP - Institut Polytechnique de Bordeaux
18 IC UM3 (UMR 8104 / U1016) - Institut Cochin
19 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
20 CHU de Grenoble UF de Biochimie Génétique et Moléculaire, 38000, Grenoble, France.
21 Grenoble Neuroscience Institute, INSERM 1216, 38000, Grenoble, France.
22 Laboratoire d'Histologie Embryologie - Biologie de la Reproduction
Serge Crouzy
  • Fonction : Auteur
  • PersonId : 963404
Jean-François Deleuze
  • Fonction : Auteur
  • PersonId : 1015006
Anne Boland
  • Fonction : Auteur
  • PersonId : 901770
Nicolas Thierry-Mieg

Résumé

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.

Dates et versions

hal-01724640 , version 1 (06-03-2018)

Identifiants

Citer

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, 2018, 9, pp.686. ⟨10.1038/s41467-017-02792-7⟩. ⟨hal-01724640⟩
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