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The channel-kinase TRPM7 regulates antigen gathering and internalization in B cells
Science Signaling ( IF 6.7 ) Pub Date : 2018-06-05 , DOI: 10.1126/scisignal.aah6692
Mithunah Krishnamoorthy 1 , Laabiah Wasim 2 , Fathima Hifza Mohamed Buhari 3 , Tiantian Zhao 2 , Trisha Mahtani 1 , Josephine Ho 3 , Sohee Kang 4 , Francina Deason-Towne 5 , Anne-Laure Perraud 5 , Carsten Schmitz 5, 6 , Bebhinn Treanor 1, 2, 3
Affiliation  

Members of the transient receptor potential (TRP) family of ion channels are cellular sensors involved in numerous physiological and pathological processes. We identified the TRP subfamily M member 7 (TRPM7) channel-kinase as a previously uncharacterized regulator of B cell activation. We showed that TRPM7 played a critical role in the early events of B cell activation through both its ion channel and kinase functions. DT40 B cells deficient in TRPM7 or expressing a kinase-deficient mutant of TRPM7 showed defective gathering of antigen and prolonged B cell receptor (BCR) signaling. We showed that lipid metabolism was altered in TRPM7-deficient cells and in cells expressing a kinase-deficient mutant of TRPM7 and suggest that PLC-γ2 may be a target of the kinase activity of TRPM7. Primary B cells that expressed less TRPM7 or were treated with a pharmacological inhibitor of TRPM7 also displayed defective antigen gathering and increased BCR signaling. Finally, we demonstrated that blocking TRPM7 function compromised antigen internalization and presentation to T cells. These data suggest that TRPM7 controls an essential process required for B cell affinity maturation and the production of high-affinity antibodies.



中文翻译:

通道激酶TRPM7调节B细胞中的抗原聚集和内在化

离子通道的瞬时受体电位(TRP)家族的成员是参与许多生理和病理过程的细胞传感器。我们确定TRP亚家族M成员7(TRPM7)通道激酶是B细胞活化的先前未知的调节剂。我们显示,TRPM7通过其离子通道和激酶功能在B细胞活化的早期事件中起着关键作用。缺乏TRPM7或表达TRPM7的激酶缺陷型突变体的DT40 B细胞显示抗原聚集不良和延长的B细胞受体(BCR)信号传导。我们发现脂质代谢在TRPM7缺陷型细胞和表达TRPM7激酶缺陷型突变体的细胞中发生了改变,并表明PLC-γ2可能是TRPM7激酶活性的目标。表达较少TRPM7或用TRPM7药理抑制剂处理的原代B细胞也显示缺陷的抗原聚集和增加的BCR信号传导。最后,我们证明了阻断TRPM7功能会损害抗原的内在化和向T细胞的呈递。这些数据表明,TRPM7控制着B细胞亲和力成熟和高亲和力抗体产生所需的基本过程。

更新日期:2018-06-06
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