Novel axonemal protein ZMYND12 interacts with TTC29 and DNAH1, and is required for male fertility and flagellum function.

Autor:	Dacheux D; University of Bordeaux, CNRS, Bordeaux, France.; Bordeaux INP, Microbiologie Fondamentale et Pathogénicité, Bordeaux, France., Martinez G; CHU Grenoble-Alpes, UM de Génétique Chromosomique, Grenoble, France., Broster Reix CE; University of Bordeaux, CNRS, Bordeaux, France., Beurois J; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Lores P; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cite, Paris, France., Tounkara M; University of Bordeaux, CNRS, Bordeaux, France., Dupuy JW; Université Bordeaux, Plateforme Protéome, Bordeaux, France., Robinson DR; University of Bordeaux, CNRS, Bordeaux, France., Loeuillet C; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Lambert E; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Wehbe Z; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Escoffier J; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Amiri-Yekta A; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Islamic Republic of Iran., Daneshipour A; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Islamic Republic of Iran., Hosseini SH; Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Islamic Republic of Iran., Zouari R; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Mustapha SFB; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Halouani L; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Jiang X; Human Sperm Bank, West China Second University Hospital of Sichuan University, Sichuan, China.; NHC Key Laboratory of Chronobiology, Sichuan University, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan, China., Shen Y; NHC Key Laboratory of Chronobiology, Sichuan University, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan, China., Liu C; Obstetrics and Gynecology Hospital, Fudan University, Fudan, China., Thierry-Mieg N; Université Grenoble Alpes, CNRS, Grenoble, France., Septier A; Université Grenoble Alpes, CNRS, Grenoble, France., Bidart M; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France.; CHU Grenoble Alpes, Laboratoire de Génétique Moléculaire: Maladies Héréditaires et Oncologie, Grenoble, France., Satre V; CHU Grenoble-Alpes, UM de Génétique Chromosomique, Grenoble, France.; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Cazin C; CHU Grenoble-Alpes, UM de Génétique Chromosomique, Grenoble, France.; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France.; CHU de Grenoble, UM GI-DPI, Grenoble, France., Kherraf ZE; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France.; CHU de Grenoble, UM GI-DPI, Grenoble, France., Arnoult C; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France., Ray PF; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France.; CHU de Grenoble, UM GI-DPI, Grenoble, France., Toure A; Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, Team Physiology and Pathophysiology of Sperm cells, Grenoble, France., Bonhivers M; University of Bordeaux, CNRS, Bordeaux, France., Coutton C; Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Team Genetics Epigenetics and Therapies of Infertility, Grenoble, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Nov 07; Vol. 12. Date of Electronic Publication: 2023 Nov 07.
DOI:	10.7554/eLife.87698
Abstrakt:	Male infertility is common and complex, presenting a wide range of heterogeneous phenotypes. Although about 50% of cases are estimated to have a genetic component, the underlying cause often remains undetermined. Here, from whole-exome sequencing on samples from 168 infertile men with asthenoteratozoospermia due to severe sperm flagellum, we identified homozygous ZMYND12 variants in four unrelated patients. In sperm cells from these individuals, immunofluorescence revealed altered localization of DNAH1, DNALI1, WDR66, and TTC29. Axonemal localization of ZMYND12 ortholog TbTAX-1 was confirmed using the Trypanosoma brucei model. RNAi knock-down of TbTAX-1 dramatically affected flagellar motility, with a phenotype similar to the sperm from men bearing homozygous ZMYND12 variants. Co-immunoprecipitation and ultrastructure expansion microscopy in T. brucei revealed TbTAX-1 to form a complex with TTC29. Comparative proteomics with samples from Trypanosoma and Ttc29 KO mice identified a third member of this complex: DNAH1. The data presented revealed that ZMYND12 is part of the same axonemal complex as TTC29 and DNAH1, which is critical for flagellum function and assembly in humans, and Trypanosoma . ZMYND12 is thus a new asthenoteratozoospermia-associated gene, bi-allelic variants of which cause severe flagellum malformations and primary male infertility. Competing Interests: DD, GM, CB, JB, PL, MT, JD, DR, CL, EL, ZW, JE, AA, AD, SH, RZ, SM, LH, XJ, YS, CL, NT, AS, MB, VS, CC, ZK, CA, PR, AT, MB, CC No competing interests declared (© 2023, Dacheux, Martinez et al.)
Databáze:	MEDLINE
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