Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans
Summary: Sperm fertilization ability mainly relies on proper sperm progression through the female genital tract and capacitation, which involves phosphorylation signaling pathways triggered by calcium and bicarbonate. We performed exome sequencing of an infertile asthenozoospermic patient and identi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223014311 |
| _version_ | 1797774474710351872 |
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| author | Emma Cavarocchi Camille Sayou Patrick Lorès Caroline Cazin Laurence Stouvenel Elma El Khouri Charles Coutton Zine-Eddine Kherraf Catherine Patrat Jérôme Govin Nicolas Thierry-Mieg Marjorie Whitfield Pierre F. Ray Emmanuel Dulioust Aminata Touré |
| author_facet | Emma Cavarocchi Camille Sayou Patrick Lorès Caroline Cazin Laurence Stouvenel Elma El Khouri Charles Coutton Zine-Eddine Kherraf Catherine Patrat Jérôme Govin Nicolas Thierry-Mieg Marjorie Whitfield Pierre F. Ray Emmanuel Dulioust Aminata Touré |
| author_sort | Emma Cavarocchi |
| collection | DOAJ |
| description | Summary: Sperm fertilization ability mainly relies on proper sperm progression through the female genital tract and capacitation, which involves phosphorylation signaling pathways triggered by calcium and bicarbonate. We performed exome sequencing of an infertile asthenozoospermic patient and identified truncating variants in MAP7D3, encoding a microtubule-associated protein, and IQCH, encoding a protein of unknown function with enzymatic and signaling features. We demonstrate the deleterious impact of both variants on sperm transcripts and proteins from the patient. We show that, in vitro, patient spermatozoa could not induce the phosphorylation cascades associated with capacitation. We also provide evidence for IQCH association with calmodulin, a well-established calcium-binding protein that regulates the calmodulin kinase. Notably, we describe IQCH spatial distribution around the sperm axoneme, supporting its function within flagella. Overall, our work highlights the cumulative pathological impact of gene mutations and identifies IQCH as a key protein required for sperm motility and capacitation. |
| first_indexed | 2024-03-12T22:21:37Z |
| format | Article |
| id | doaj.art-4849c1c8f2ce49cba28ea421e079c4d2 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:21:37Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4849c1c8f2ce49cba28ea421e079c4d22023-07-23T04:56:08ZengElsevieriScience2589-00422023-08-01268107354Identification of IQCH as a calmodulin-associated protein required for sperm motility in humansEmma Cavarocchi0Camille Sayou1Patrick Lorès2Caroline Cazin3Laurence Stouvenel4Elma El Khouri5Charles Coutton6Zine-Eddine Kherraf7Catherine Patrat8Jérôme Govin9Nicolas Thierry-Mieg10Marjorie Whitfield11Pierre F. Ray12Emmanuel Dulioust13Aminata Touré14Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, FranceInstitut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cité, 75014 Paris, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU de Grenoble Alpes, UM GI-DPI, 38000 Grenoble, FranceInstitut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cité, 75014 Paris, FranceInstitut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cité, 75014 Paris, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU Grenoble Alpes, UM de Génétique Chromosomique, Grenoble, FranceCHU de Grenoble Alpes, UM GI-DPI, 38000 Grenoble, FranceInstitut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cité, 75014 Paris, France; Laboratoire d’Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, FranceUniversity Grenoble Alpes, CNRS, UMR 5525, TIMC / MAGe, 38000 Grenoble, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; CHU de Grenoble Alpes, UM GI-DPI, 38000 Grenoble, FranceInstitut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Cité, 75014 Paris, France; Laboratoire d’Histologie Embryologie - Biologie de la Reproduction - CECOS Groupe Hospitalier Universitaire Paris Centre, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceInstitute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; Corresponding authorSummary: Sperm fertilization ability mainly relies on proper sperm progression through the female genital tract and capacitation, which involves phosphorylation signaling pathways triggered by calcium and bicarbonate. We performed exome sequencing of an infertile asthenozoospermic patient and identified truncating variants in MAP7D3, encoding a microtubule-associated protein, and IQCH, encoding a protein of unknown function with enzymatic and signaling features. We demonstrate the deleterious impact of both variants on sperm transcripts and proteins from the patient. We show that, in vitro, patient spermatozoa could not induce the phosphorylation cascades associated with capacitation. We also provide evidence for IQCH association with calmodulin, a well-established calcium-binding protein that regulates the calmodulin kinase. Notably, we describe IQCH spatial distribution around the sperm axoneme, supporting its function within flagella. Overall, our work highlights the cumulative pathological impact of gene mutations and identifies IQCH as a key protein required for sperm motility and capacitation.http://www.sciencedirect.com/science/article/pii/S2589004223014311Health sciencesClinical geneticsCell biology |
| spellingShingle | Emma Cavarocchi Camille Sayou Patrick Lorès Caroline Cazin Laurence Stouvenel Elma El Khouri Charles Coutton Zine-Eddine Kherraf Catherine Patrat Jérôme Govin Nicolas Thierry-Mieg Marjorie Whitfield Pierre F. Ray Emmanuel Dulioust Aminata Touré Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans iScience Health sciences Clinical genetics Cell biology |
| title | Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans |
| title_full | Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans |
| title_fullStr | Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans |
| title_full_unstemmed | Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans |
| title_short | Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans |
| title_sort | identification of iqch as a calmodulin associated protein required for sperm motility in humans |
| topic | Health sciences Clinical genetics Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223014311 |
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