Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis
Hereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.960291/full |
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| author | Alexis Caulier Nicolas Jankovsky Emilie Fleur Gautier Emilie Fleur Gautier Emilie Fleur Gautier Wassim El Nemer Corinne Guitton Hakim Ouled-Haddou François Guillonneau Patrick Mayeux Virginie Salnot Johanna Bruce Véronique Picard Véronique Picard Loïc Garçon Loïc Garçon Loïc Garçon |
| author_facet | Alexis Caulier Nicolas Jankovsky Emilie Fleur Gautier Emilie Fleur Gautier Emilie Fleur Gautier Wassim El Nemer Corinne Guitton Hakim Ouled-Haddou François Guillonneau Patrick Mayeux Virginie Salnot Johanna Bruce Véronique Picard Véronique Picard Loïc Garçon Loïc Garçon Loïc Garçon |
| author_sort | Alexis Caulier |
| collection | DOAJ |
| description | Hereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain of function mutations in PIEZO1, encoding a mechanotransductor that translates a mechanical stimulus into a biological signaling. Data are still required to understand better PIEZO1-HX pathophysiology. Recent studies identified proteomics as an accurate and high-input tool to study erythroid progenitors and circulating red cell physiology. Here, we isolated red blood cells from 5 controls and 5 HX patients carrying an identified and pathogenic PIEZO1 mutation and performed a comparative deep proteomic analysis. A total of 603 proteins were identified among which 56 were differentially expressed (40 over expressed and 16 under expressed) between controls and HX with a homogenous expression profile within each group. We observed relevant modifications in the protein expression profile related to PIEZO1 mutations, identifying two main “knots”. The first contained both proteins of the chaperonin containing TCP1 complex involved in the assembly of unfolded proteins, and proteins involved in translation. The second contained proteins involved in ubiquitination. Deregulation of proteins involved in protein biosynthesis was also observed in in vitro-produced reticulocytes after Yoda1 exposure. Thus, our work identifies significant changes in the protein content of PIEZO1-HX erythrocytes, revealing a “PIEZO1 signature” and identifying potentially targetable pathways in this disease characterized by a heterogeneous clinical expression and contra-indication of splenectomy. |
| first_indexed | 2024-04-13T13:00:26Z |
| format | Article |
| id | doaj.art-41d3e8f282a840d9adfbdf38314def55 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-13T13:00:26Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-41d3e8f282a840d9adfbdf38314def552022-12-22T02:45:56ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-12-011310.3389/fphys.2022.960291960291Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosisAlexis Caulier0Nicolas Jankovsky1Emilie Fleur Gautier2Emilie Fleur Gautier3Emilie Fleur Gautier4Wassim El Nemer5Corinne Guitton6Hakim Ouled-Haddou7François Guillonneau8Patrick Mayeux9Virginie Salnot10Johanna Bruce11Véronique Picard12Véronique Picard13Loïc Garçon14Loïc Garçon15Loïc Garçon16HEMATIM, CURS, Amiens and Laboratoire d’Hématologie, CHU Amiens, UPJV, Amiens, FranceHEMATIM, CURS, Amiens and Laboratoire d’Hématologie, CHU Amiens, UPJV, Amiens, France3P5 Proteom’IC, Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, FranceInstitut Imagine-INSERM U1163, Necker Hospital, University of Paris, Paris, FranceLaboratoire d’excellence GR-Ex, Paris, FranceINSERM U1134, INTS, Paris, FranceLaboratoire d’Hématologie et Filière MCGRE, CHU Bicêtre, Le Kremlin-Bicêtre, FranceHEMATIM, CURS, Amiens and Laboratoire d’Hématologie, CHU Amiens, UPJV, Amiens, France3P5 Proteom’IC, Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, France3P5 Proteom’IC, Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, France3P5 Proteom’IC, Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, France3P5 Proteom’IC, Institut Cochin, INSERM, CNRS, Université Paris Cité, Paris, FranceLaboratoire d’Hématologie et Filière MCGRE, CHU Bicêtre, Le Kremlin-Bicêtre, FranceLaboratoire d’Hématologie, Faculté de Pharmacie, Université Paris Saclay, Amiens, FranceHEMATIM, CURS, Amiens and Laboratoire d’Hématologie, CHU Amiens, UPJV, Amiens, FranceINSERM U1134, INTS, Paris, FranceLaboratoire d’Hématologie et Filière MCGRE, CHU Bicêtre, Le Kremlin-Bicêtre, FranceHereditary xerocytosis is a dominant red cell membrane disorder characterized by an increased leak of potassium from the inside to outside the red blood cell membrane, associated with loss of water leading to red cell dehydration and chronic hemolysis. 90% of cases are related to heterozygous gain of function mutations in PIEZO1, encoding a mechanotransductor that translates a mechanical stimulus into a biological signaling. Data are still required to understand better PIEZO1-HX pathophysiology. Recent studies identified proteomics as an accurate and high-input tool to study erythroid progenitors and circulating red cell physiology. Here, we isolated red blood cells from 5 controls and 5 HX patients carrying an identified and pathogenic PIEZO1 mutation and performed a comparative deep proteomic analysis. A total of 603 proteins were identified among which 56 were differentially expressed (40 over expressed and 16 under expressed) between controls and HX with a homogenous expression profile within each group. We observed relevant modifications in the protein expression profile related to PIEZO1 mutations, identifying two main “knots”. The first contained both proteins of the chaperonin containing TCP1 complex involved in the assembly of unfolded proteins, and proteins involved in translation. The second contained proteins involved in ubiquitination. Deregulation of proteins involved in protein biosynthesis was also observed in in vitro-produced reticulocytes after Yoda1 exposure. Thus, our work identifies significant changes in the protein content of PIEZO1-HX erythrocytes, revealing a “PIEZO1 signature” and identifying potentially targetable pathways in this disease characterized by a heterogeneous clinical expression and contra-indication of splenectomy.https://www.frontiersin.org/articles/10.3389/fphys.2022.960291/fullxeroxytosisproteomicspiezo1 channelubiquitinred blood cell |
| spellingShingle | Alexis Caulier Nicolas Jankovsky Emilie Fleur Gautier Emilie Fleur Gautier Emilie Fleur Gautier Wassim El Nemer Corinne Guitton Hakim Ouled-Haddou François Guillonneau Patrick Mayeux Virginie Salnot Johanna Bruce Véronique Picard Véronique Picard Loïc Garçon Loïc Garçon Loïc Garçon Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis Frontiers in Physiology xeroxytosis proteomics piezo1 channel ubiquitin red blood cell |
| title | Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis |
| title_full | Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis |
| title_fullStr | Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis |
| title_full_unstemmed | Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis |
| title_short | Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis |
| title_sort | red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in piezo1 related hereditary xerocytosis |
| topic | xeroxytosis proteomics piezo1 channel ubiquitin red blood cell |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.960291/full |
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