Lack of CCDC146, a ubiquitous centriole and microtubule-associated protein, leads to non-syndromic male infertility in human and mouse.

Autor:	Muroňová J; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Kherraf ZE; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; UM GI-DPI, CHU Grenoble Alpes, Grenoble, France., Giordani E; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Lambert E; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Eckert S; Cell Biology/ Electron Microscopy, University of Bayreuth, Bayreuth, Germany., Cazin C; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; UM GI-DPI, CHU Grenoble Alpes, Grenoble, France., Amiri-Yekta A; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Islamic Republic of Iran., Court M; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Chevalier G; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Martinez G; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; UM de Génétique Chromosomique, Hôpital Couple-Enfant, CHU Grenoble Alpes, Grenoble, France., Neirijnck Y; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland., Kühne F; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland., Wehrli L; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland., Klena N; University of Geneva, Department of Molecular and Cellular Biology, Sciences III, Geneva, Switzerland., Hamel V; University of Geneva, Department of Molecular and Cellular Biology, Sciences III, Geneva, Switzerland., De Macedo L; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Escoffier J; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Guichard P; University of Geneva, Department of Molecular and Cellular Biology, Sciences III, Geneva, Switzerland., Coutton C; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; UM de Génétique Chromosomique, Hôpital Couple-Enfant, CHU Grenoble Alpes, Grenoble, France., Mustapha SFB; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Kharouf M; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Bouin AP; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Zouari R; Polyclinique les Jasmins, Centre d'Aide Médicale à la Procréation, Centre Urbain Nord, Tunis, Tunisia., Thierry-Mieg N; Laboratoire TIMC/MAGe, CNRS UMR 5525, Pavillon Taillefer, Faculté de Medecine, La Tronche, France., Nef S; Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland., Geimer S; Cell Biology/ Electron Microscopy, University of Bayreuth, Bayreuth, Germany., Loeuillet C; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France., Ray PF; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.; UM GI-DPI, CHU Grenoble Alpes, Grenoble, France., Arnoult C; Institute for Advanced Biosciences (IAB), INSERM 1209, Grenoble, France.; Institute for Advanced Biosciences (IAB), CNRS UMR 5309, Grenoble, France.; Institute for Advanced Biosciences (IAB), Université Grenoble Alpes, Grenoble, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Mar 05; Vol. 12. Date of Electronic Publication: 2024 Mar 05.
DOI:	10.7554/eLife.86845
Abstrakt:	From a cohort of 167 infertile patients suffering from multiple morphological abnormalities of the flagellum (MMAF), pathogenic bi-allelic mutations were identified in the CCDC146 gene. In somatic cells, CCDC146 is located at the centrosome and at multiple microtubule-related organelles during mitotic division, suggesting that it is a microtubule-associated protein (MAP). To decipher the molecular pathogenesis of infertility associated with CCDC146 mutations, a Ccdc146 knock-out (KO) mouse line was created. KO male mice were infertile, and sperm exhibited a phenotype identical to CCDC146 mutated patients. CCDC146 expression starts during late spermiogenesis. In the spermatozoon, the protein is conserved but is not localized to centrioles, unlike in somatic cells, rather it is present in the axoneme at the level of microtubule doublets. Expansion microscopy associated with the use of the detergent sarkosyl to solubilize microtubule doublets suggests that the protein may be a microtubule inner protein (MIP). At the subcellular level, the absence of CCDC146 impacted all microtubule-based organelles such as the manchette, the head-tail coupling apparatus (HTCA), and the axoneme. Through this study, a new genetic cause of infertility and a new factor in the formation and/or structure of the sperm axoneme were characterized. Competing Interests: JM, ZK, EG, EL, SE, CC, AA, MC, GC, GM, YN, FK, LW, NK, VH, LD, JE, PG, CC, SM, MK, AB, RZ, NT, SN, SG, CL, PR, CA No competing interests declared (© 2023, Muroňová, Kherraf et al.)
Databáze:	MEDLINE
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