Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels
| Autor: | Jean Pierre De Jaureguiberry, Pierre-Simon Rohrlich, Loïc Garçon, Gérard Tertian, Swetha E. Murthy, Madeleine Fénéant-Thibault, Michael Bandell, Xavier Jeunemaitre, Fabienne Toutain, Véronique Picard, Bertrand Coste, Juliette Albuisson, Pierre Yves Syfuss, Stuart M. Cahalan, Ardem Patapoutian, Hélène Louis-Dit-Picard, Jean Delaunay, Jayanti Mathur |
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| Přispěvatelé: | Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Molecular and Cellular Neuroscience Department, The Scripps Research Institute-Dorris Neuroscience Center, Novartis Research Foundation, Service de Biochimie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Ingénierie des protéines de l'hémostase à potentiel thérapeutique, Université Paris-Sud - Paris 11 (UP11), Hématologie biologique [CHU Bicêtre], Centre Hospitalier Sainte Anne [Paris], CH de Troyes, Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pontchaillou [Rennes], Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), HAL UPMC, Gestionnaire, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Scripps Research Institute [La Jolla, San Diego]-Dorris Neuroscience Center, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) |
| Rok vydání: | 2013 |
| Předmět: |
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
Male Hydrops Fetalis DNA Mutational Analysis General Physics and Astronomy Ion Channels 0302 clinical medicine Gene duplication [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology Missense mutation Mechanotransduction [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics Child 0303 health sciences Multidisciplinary [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Middle Aged Phenotype Recombinant Proteins Biomechanical Phenomena Pedigree 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Dehydrated hereditary stomatocytosis Female Hydrophobic and Hydrophilic Interactions Ion Channel Gating Adult Adolescent Molecular Sequence Data [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics Biology Anemia Hemolytic Congenital Article General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences medicine Humans Amino Acid Sequence Ion channel Aged 030304 developmental biology PIEZO1 General Chemistry Molecular biology Kinetics Red blood cell [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Mutation |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2013, 4 (1), pp.1884. ⟨10.1038/ncomms2899⟩ Nature communications Nature Communications, 2013, 4 (1), pp.1884. ⟨10.1038/ncomms2899⟩ Nature Communications, Nature Publishing Group, 2013, 4, pp.1884. 〈10.1038/ncomms2899〉 |
| ISSN: | 2041-1723 |
| Popis: | International audience; Dehydrated hereditary stomatocytosis is a genetic condition with defective red blood cell membrane properties that causes an imbalance in intracellular cation concentrations. Recently, two missense mutations in the mechanically activated PIEZO1 (FAM38A) ion channel were associated with dehydrated hereditary stomatocytosis. However, it is not known how these mutations affect PIEZO1 function. Here, by combining linkage analysis and whole-exome sequencing in a large pedigree and Sanger sequencing in two additional kindreds and 11 unrelated dehydrated hereditary stomatocytosis cases, we identify three novel missense mutations and one recurrent duplication in PIEZO1, demonstrating that it is the major gene for dehydrated hereditary stomatocytosis. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of PIEZO1. Remarkably, we find that all PIEZO1 mutations give rise to mechanically activated currents that inactivate more slowly than wild-type currents. This gain-of-function PIEZO1 phenotype provides insight that helps to explain the increased permeability of cations in red blood cells of dehydrated hereditary stomatocytosis patients. Our findings also suggest a new role for mechanotransduction in red blood cell biology and pathophysiology. |
| Databáze: | OpenAIRE |
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