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Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens
Despite the identification of the high-incidence red cell antigen Er(a) nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically def...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644042/ https://www.ncbi.nlm.nih.gov/pubmed/36122374 http://dx.doi.org/10.1182/blood.2022016504 |
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author | Karamatic Crew, Vanja Tilley, Louise A. Satchwell, Timothy J. AlSubhi, Samah A. Jones, Benjamin Spring, Frances A. Walser, Piers J. Martins Freire, Catarina Murciano, Nicoletta Rotordam, Maria Giustina Woestmann, Svenja J. Hamed, Marwa Alradwan, Reem AlKhrousey, Mouza Skidmore, Ian Lewis, Sarah Hussain, Shimon Jackson, Jane Latham, Tom Kilby, Mark D. Lester, William Becker, Nadine Rapedius, Markus Toye, Ashley M. Thornton, Nicole M. |
author_facet | Karamatic Crew, Vanja Tilley, Louise A. Satchwell, Timothy J. AlSubhi, Samah A. Jones, Benjamin Spring, Frances A. Walser, Piers J. Martins Freire, Catarina Murciano, Nicoletta Rotordam, Maria Giustina Woestmann, Svenja J. Hamed, Marwa Alradwan, Reem AlKhrousey, Mouza Skidmore, Ian Lewis, Sarah Hussain, Shimon Jackson, Jane Latham, Tom Kilby, Mark D. Lester, William Becker, Nadine Rapedius, Markus Toye, Ashley M. Thornton, Nicole M. |
author_sort | Karamatic Crew, Vanja |
collection | PubMed |
description | Despite the identification of the high-incidence red cell antigen Er(a) nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line. We report the molecular bases of 5 Er blood group antigens: the recognized Er(a), Er(b), and Er3 antigens and 2 novel high-incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn. Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low-abundance membrane proteins and contributes to our understanding of the in vivo characteristics of this important and widely studied protein in transfusion biology and beyond. |
format | Online Article Text |
id | pubmed-10644042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106440422023-11-14 Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens Karamatic Crew, Vanja Tilley, Louise A. Satchwell, Timothy J. AlSubhi, Samah A. Jones, Benjamin Spring, Frances A. Walser, Piers J. Martins Freire, Catarina Murciano, Nicoletta Rotordam, Maria Giustina Woestmann, Svenja J. Hamed, Marwa Alradwan, Reem AlKhrousey, Mouza Skidmore, Ian Lewis, Sarah Hussain, Shimon Jackson, Jane Latham, Tom Kilby, Mark D. Lester, William Becker, Nadine Rapedius, Markus Toye, Ashley M. Thornton, Nicole M. Blood Plenary Paper Despite the identification of the high-incidence red cell antigen Er(a) nearly 40 years ago, the molecular background of this antigen, together with the other 2 members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout, and expression studies in an erythroblast cell line. We report the molecular bases of 5 Er blood group antigens: the recognized Er(a), Er(b), and Er3 antigens and 2 novel high-incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn. Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low-abundance membrane proteins and contributes to our understanding of the in vivo characteristics of this important and widely studied protein in transfusion biology and beyond. The American Society of Hematology 2023-01-12 2022-09-21 /pmc/articles/PMC10644042/ /pubmed/36122374 http://dx.doi.org/10.1182/blood.2022016504 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Plenary Paper Karamatic Crew, Vanja Tilley, Louise A. Satchwell, Timothy J. AlSubhi, Samah A. Jones, Benjamin Spring, Frances A. Walser, Piers J. Martins Freire, Catarina Murciano, Nicoletta Rotordam, Maria Giustina Woestmann, Svenja J. Hamed, Marwa Alradwan, Reem AlKhrousey, Mouza Skidmore, Ian Lewis, Sarah Hussain, Shimon Jackson, Jane Latham, Tom Kilby, Mark D. Lester, William Becker, Nadine Rapedius, Markus Toye, Ashley M. Thornton, Nicole M. Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title | Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title_full | Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title_fullStr | Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title_full_unstemmed | Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title_short | Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens |
title_sort | missense mutations in piezo1, which encodes the piezo1 mechanosensor protein, define er red blood cell antigens |
topic | Plenary Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644042/ https://www.ncbi.nlm.nih.gov/pubmed/36122374 http://dx.doi.org/10.1182/blood.2022016504 |
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