Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens.
Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens.
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编码压电1机械传感器蛋白的压电1中的错义突变定义了红细胞抗原。
DOI：
10.1182/blood.2022016504
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发表时间：
2023-01-12
期刊：
影响因子：
20.3
通讯作者：
Thornton, Nicole M.
中科院分区：
文献类型：
--
作者：
Crew, Vanja Karamatic;Tilley, Louise A.;Satchwell, Timothy J.;AlSubhi, Samah A.;Jones, Benjamin;Spring, Frances A.;Walser, Piers J.;Freire, Catarina Martins;Murciano, Nicoletta;Rotordam, Maria Giustina;Woestmann, Svenja J.;Hamed, Marwa;Alradwan, Reem;AlKhrousey, Mouza;Skidmore, Ian;Lewis, Sarah;Hussain, Shimon;Jackson, Jane;Latham, Tom;Kiloy, Mark D.;Lester, William;Becker, Nadine;Rapedius, Markus;Toye, Ashley M.;Thornton, Nicole M.
机械感觉离子通道Piezo 1是Er红细胞抗原的载体分子，建立了新的血型系统。针对2种新的高发病率Er抗原的抗体与胎儿和新生儿的严重溶血性疾病相关。尽管近40年前鉴定出了高发病率的红细胞抗原Era，但该抗原以及Er血型集合的其他2个成员的分子背景尚未阐明。全外显子组和桑格测序的个人与血清学定义的Er同种抗体确定了几个错义突变的PIEZO 1基因内，编码氨基酸取代的Piezo 1机械传感器离子通道的细胞外结构域。使用免疫沉淀、CRISPR/Cas9介导的基因敲除和成红细胞系中的表达研究证实了Piezo 1作为Er血型抗原的载体分子。我们报告了5个Er血型抗原的分子基础：公认的Era，Erb和Er 3抗原和2个新的高发病率Er抗原，这里描述为Er 4和Er 5，建立一个新的血型系统。抗Er 4和抗Er 5与胎儿和新生儿的严重溶血性疾病有关。Piezo 1在红细胞表面仅存在几百个拷贝，作为新血型系统的位点，这一证明突出了即使是低丰度膜蛋白的潜在抗原性，并有助于我们了解这种重要且在输血生物学及其他领域广泛研究的蛋白质的体内特征。Crew等人解决了红细胞生物学和输血医学中一个长期存在的谜团，即Er血型抗原的分子和遗传学阐明。通过分析同种抗体数据和全外显子组测序，作者将这些抗原定位于机械感觉蛋白PEIZO 1。此外，他们报告了针对2种新的、高度流行的Er抗原的抗体与胎儿和新生儿的严重溶血性疾病相关。
The mechanosensory ion channel Piezo1 is the carrier molecule for Er red cell antigens, establishing a new blood group system. Antibodies directed against 2 novel high-incidence Er antigens are associated with severe hemolytic disease of the fetus and newborn. Despite the identification of the high-incidence red cell antigen Era 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 Era, Erb, 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. Crew et al solve a long-standing enigma in red cell biology and transfusion medicine, namely the molecular and genetic elucidation of the Er blood group antigens. Through analysis of alloantibody data and whole exome sequencing, the authors localize these antigens to the mechanosensory protein PEIZO1. Furthermore, they report that antibodies directed against 2 novel, highly prevalent Er antigens are associated with severe hemolytic disease of the fetus and newborn.
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影响因子：
7.5
作者：
Gautier, Emilie-Fleur;Leduc, Marjorie;Mayeux, Patrick
通讯作者：
Mayeux, Patrick
DOI：
10.1093/dnares/3.5.321
发表时间：
1996-10-31
期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子：
--
作者：
Nagase, T;Seki, N;Nomura, N
通讯作者：
Nomura, N
遗传性红细胞疾病中遗传的复杂模式：155例患者的病例系列研究。
影响因子：
3.5
作者：
Andolfo I;Martone S;Rosato BE;Marra R;Gambale A;Forni GL;Pinto V;Göransson M;Papadopoulou V;Gavillet M;Elalfy M;Panarelli A;Tomaiuolo G;Iolascon A;Russo R
通讯作者：
Russo R
影响因子：
64.5
作者：
Ma S;Dubin AE;Zhang Y;Mousavi SAR;Wang Y;Coombs AM;Loud M;Andolfo I;Patapoutian A
通讯作者：
Patapoutian A
影响因子：
11.1
作者：
Hawksworth J;Satchwell TJ;Meinders M;Daniels DE;Regan F;Thornton NM;Wilson MC;Dobbe JG;Streekstra GJ;Trakarnsanga K;Heesom KJ;Anstee DJ;Frayne J;Toye AM
通讯作者：
Toye AM