Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B‐cell development and Ca2+ homeostasis in mice,European Journal of Immunology

当前位置： X-MOL 学术 › Eur. J. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B‐cell development and Ca2+ homeostasis in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-10-24 , DOI: 10.1002/eji.202048654
Mark Korthals ₁ , Laura Tech ₁ , Kristina Langnaese ₁ , Anna Gottfried ₁ , Johannes Hradsky ₁ , Ulrich Thomas ₂ , Ana Claudia Zenclussen ₃ , Monika C Brunner-Weinzierl ₄ , Kerry Tedford ₁ , Klaus-Dieter Fischer ₁

Affiliation

The amplitude and duration of Ca²⁺ signaling is crucial for B‐cell development and self‐tolerance; however, the mechanisms for terminating Ca²⁺ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca²⁺ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca²⁺ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B‐cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B‐1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4^−/− B cells, but Pmca1 KO B cells had elevated basal levels of Ca²⁺, elevated levels in ER stores, and reduced Ca²⁺ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B‐cell Ca²⁺ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca²⁺ in B cells.

中文翻译：

质膜 Ca2+ ATPase 1 (PMCA1) 但不是 PMCA4 对小鼠的 B 细胞发育和 Ca2+ 稳态至关重要

Ca ²⁺信号的幅度和持续时间对 B 细胞发育和自我耐受至关重要；然而，终止B 细胞中Ca ²⁺信号的机制尚未确定。在淋巴细胞中，质膜 Ca ²⁺ ATPase (PMCA) 亚型 1 和 4（PMCA1 和 PMCA4，又名 ATP2B1 和 ATP2B4）是通过质膜从细胞中排出 Ca ²⁺的主要候选物。我们在此报告Pmca4 ( Atp2b4 ) KO 小鼠的 B 细胞发育正常，而Pmca1 ( Atp2b1) 的 B 细胞数量大大减少，特别是脾滤泡 B 细胞、边缘区 B 细胞和腹膜 B-1a 细胞。与表达 PMCA4 的 T 细胞相比，小鼠和初始人类 B 细胞通过蛋白质印迹仅显示 PMCA1 表达而未显示 PMCA4。Pmca4 ^-/- B 细胞的钙处理正常，但Pmca1 KO B 细胞的基础 Ca ²⁺水平升高，ER 储存水平升高，Ca ²⁺清除率降低。这些发现表明，仅需要 PMCA1 亚型来确保正常的 B 细胞 Ca ²⁺信号传导和发育，这可能对B 细胞中 PMCA 和 Ca ^{2+ 的}治疗靶向有影响。

更新日期：2020-10-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11